rs6067

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP7BP4BA1

This summary comes from the ClinGen Evidence Repository: The synonymous variant NM_000173.7(GP1BA):c.1074A>G (p.Arg358=) is not predicted by SpliceAI to impact splicing (score 0.00; BP4). In addition, it occurs at a nucleotide that is not highly conserved as shown by phyloP score of 0.134386 (BP7). The Grpmax Filtering allele frequency in gnomAD v4.1 is 0.2116 (based on 9653/44866 alleles, including 1018 homozygotes) in the East Asian population, which is higher than the ClinGen PD VCEP threshold (>0.001; BA1). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Bernard-Soulier syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP4, BP7 (ClinGen Platelet Disorders VCEP specifications version 1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA8314893/MONDO:0009276/079

Frequency

Genomes: 𝑓 0.049 ( 318 hom., cov: 31)

Exomes 𝑓: 0.045 ( 2660 hom. )

Consequence

GP1BA
NM_000173.7 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:4

Conservation

PhyloP100: 0.334

Publications

10 publications found

Variant links:

Genes affected

GP1BA (HGNC:4439): (glycoprotein Ib platelet subunit alpha) Glycoprotein Ib (GP Ib) is a platelet surface membrane glycoprotein composed of a heterodimer, an alpha chain and a beta chain, that is linked by disulfide bonds. The Gp Ib functions as a receptor for von Willebrand factor (VWF). The complete receptor complex includes noncovalent association of the alpha and beta subunits with platelet glycoprotein IX and platelet glycoprotein V. The binding of the GP Ib-IX-V complex to VWF facilitates initial platelet adhesion to vascular subendothelium after vascular injury, and also initiates signaling events within the platelet that lead to enhanced platelet activation, thrombosis, and hemostasis. This gene encodes the alpha subunit. Mutations in this gene result in Bernard-Soulier syndromes and platelet-type von Willebrand disease. The coding region of this gene is known to contain a polymophic variable number tandem repeat (VNTR) domain that is associated with susceptibility to nonarteritic anterior ischemic optic neuropathy. [provided by RefSeq, Oct 2013]

GP1BA links:

CHRNE (HGNC:1966): (cholinergic receptor nicotinic epsilon subunit) Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]

CHRNE Gene-Disease associations (from GenCC):

congenital myasthenic syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina
congenital myasthenic syndrome 4A
Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
congenital myasthenic syndrome 4B
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
congenital myasthenic syndrome 4C
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHRNE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

For more information check the summary or visit ClinGen Evidence Repository.

BP7

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP1BA	NM_000173.7 link	c.1074A>G	p.Arg358Arg	synonymous_variant	Exon 2 of 2	ENST00000329125.6	NP_000164.5	P07359L7UYB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP1BA	ENST00000329125.6 link	c.1074A>G	p.Arg358Arg	synonymous_variant	Exon 2 of 2	1	NM_000173.7	ENSP00000329380.5		P07359
CHRNE	ENST00000649830.1 link	c.-888+664T>C		intron_variant	Intron 1 of 10			ENSP00000496907.1		A0A3B3IRM1

Frequencies

GnomAD3 genomes

AF:

0.0487

AC:

7400

AN:

152040

Hom.:

318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.0952

Gnomad FIN

AF:

0.0240

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0344

Gnomad OTH

AF:

0.0517

GnomAD2 exomes

AF:

0.0692

AC:

17253

AN:

249270

AF XY:

0.0669

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.0575

Gnomad EAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.0255

Gnomad NFE exome

AF:

0.0345

Gnomad OTH exome

AF:

0.0638

GnomAD4 exome

AF:

0.0452

AC:

66052

AN:

1461678

Hom.:

2660

Cov.:

AF XY:

0.0465

AC XY:

33793

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.0269

AC:

901

AN:

33480

American (AMR)

AF:

0.135

AC:

6056

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0565

AC:

1477

AN:

26136

East Asian (EAS)

AF:

0.215

AC:

8546

AN:

39700

South Asian (SAS)

AF:

0.0925

AC:

7981

AN:

86252

European-Finnish (FIN)

AF:

0.0267

AC:

1425

AN:

53402

Middle Eastern (MID)

AF:

0.0741

AC:

427

AN:

5766

European-Non Finnish (NFE)

AF:

0.0323

AC:

35862

AN:

1111846

Other (OTH)

AF:

0.0559

AC:

3377

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

4661

9323

13984

18646

23307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1530

3060

4590

6120

7650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0486

AC:

7401

AN:

152158

Hom.:

318

Cov.:

AF XY:

0.0516

AC XY:

3836

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0265

AC:

1100

AN:

41478

American (AMR)

AF:

0.122

AC:

1858

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0484

AC:

168

AN:

3472

East Asian (EAS)

AF:

0.214

AC:

1107

AN:

5166

South Asian (SAS)

AF:

0.0942

AC:

454

AN:

4818

European-Finnish (FIN)

AF:

0.0240

AC:

255

AN:

10614

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0344

AC:

2338

AN:

68002

Other (OTH)

AF:

0.0502

AC:

106

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

351

703

1054

1406

1757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0443

Hom.:

153

Bravo

AF:

0.0552

Asia WGS

AF:

0.128

AC:

444

AN:

3478

EpiCase

AF:

0.0374

EpiControl

AF:

0.0373

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:2

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bernard Soulier syndrome

Benign:1

Feb 11, 2025

ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

The synonymous variant NM_000173.7(GP1BA):c.1074A>G (p.Arg358=) is not predicted by SpliceAI to impact splicing (score 0.00; BP4). In addition, it occurs at a nucleotide that is not highly conserved as shown by phyloP score of 0.134386 (BP7). The Grpmax Filtering allele frequency in gnomAD v4.1 is 0.2116 (based on 9653/44866 alleles, including 1018 homozygotes) in the East Asian population, which is higher than the ClinGen PD VCEP threshold (>0.001; BA1). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Bernard-Soulier syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP4, BP7 (ClinGen Platelet Disorders VCEP specifications version 1). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.9

(source)

DANN

Benign

0.77

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over