rs7560774

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000079.4(CHRNA1):c.43+59G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,553,240 control chromosomes in the GnomAD database, including 161,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11733 hom., cov: 32)

Exomes 𝑓: 0.45 ( 149550 hom. )

Consequence

CHRNA1
NM_000079.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.779

Publications

8 publications found

Variant links:

Genes affected

CHRNA1 (HGNC:1955): (cholinergic receptor nicotinic alpha 1 subunit) The muscle acetylcholine receptor consiststs of 5 subunits of 4 different types: 2 alpha subunits and 1 each of the beta, gamma, and delta subunits. This gene encodes an alpha subunit that plays a role in acetlycholine binding/channel gating. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2012]

CHRNA1 Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 1A
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
lethal multiple pterygium syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
myasthenic syndrome, congenital, 1B, fast-channel
Inheritance: AR, AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHRNA1 links:

ENSG00000236449 (HGNC:):

ENSG00000236449 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-174764293-C-A is Benign according to our data. Variant chr2-174764293-C-A is described in ClinVar as Benign. ClinVar VariationId is 680121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA1	NM_000079.4 link	c.43+59G>T		intron_variant	Intron 1 of 8	ENST00000348749.9	NP_000070.1
CHRNA1	NM_001039523.3 link	c.43+59G>T		intron_variant	Intron 1 of 9		NP_001034612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA1	ENST00000348749.9 link	c.43+59G>T		intron_variant	Intron 1 of 8	1	NM_000079.4	ENSP00000261008.5

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54647

AN:

151930

Hom.:

11737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.463

Gnomad AMR

AF:

0.432

Gnomad ASJ

AF:

0.531

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.423

Gnomad NFE

AF:

0.477

Gnomad OTH

AF:

0.410

GnomAD4 exome

AF:

0.453

AC:

634385

AN:

1401190

Hom.:

149550

AF XY:

0.448

AC XY:

312271

AN XY:

696458

show subpopulations

African (AFR)

AF:

0.108

AC:

3466

AN:

32098

American (AMR)

AF:

0.410

AC:

17016

AN:

41468

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

13788

AN:

25354

East Asian (EAS)

AF:

0.216

AC:

8246

AN:

38114

South Asian (SAS)

AF:

0.266

AC:

21754

AN:

81714

European-Finnish (FIN)

AF:

0.481

AC:

24739

AN:

51390

Middle Eastern (MID)

AF:

0.443

AC:

2519

AN:

5686

European-Non Finnish (NFE)

AF:

0.485

AC:

517420

AN:

1067126

Other (OTH)

AF:

0.437

AC:

25437

AN:

58240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

16983

33967

50950

67934

84917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14924

29848

44772

59696

74620

<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:

0.359

AC:

54657

AN:

152050

Hom.:

11733

Cov.:

AF XY:

0.356

AC XY:

26440

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.123

AC:

5117

AN:

41492

American (AMR)

AF:

0.432

AC:

6607

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

1840

AN:

3464

East Asian (EAS)

AF:

0.205

AC:

1060

AN:

5168

South Asian (SAS)

AF:

0.251

AC:

1210

AN:

4812

European-Finnish (FIN)

AF:

0.477

AC:

5031

AN:

10556

Middle Eastern (MID)

AF:

0.414

AC:

120

AN:

290

European-Non Finnish (NFE)

AF:

0.477

AC:

32394

AN:

67960

Other (OTH)

AF:

0.407

AC:

858

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1596

3192

4787

6383

7979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<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:

0.455

Hom.:

12611

Bravo

AF:

0.349

Asia WGS

AF:

0.221

AC:

771

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Myasthenic syndrome, congenital, 1B, fast-channel

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lethal multiple pterygium syndrome

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital myasthenic syndrome 1A

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.90

(source)

DANN

Benign

0.70

PhyloP100

-0.78

PromoterAI

-0.0033

Neutral

(source)

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