rs4900

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002067.5(GNA11):c.771C>T(p.Thr257Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,612,358 control chromosomes in the GnomAD database, including 172,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 12144 hom., cov: 32)

Exomes 𝑓: 0.47 ( 160274 hom. )

Consequence

GNA11
NM_002067.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.579

Publications

33 publications found

Variant links:

Genes affected

GNA11 (HGNC:4379): (G protein subunit alpha 11) The protein encoded by this gene belongs to the family of guanine nucleotide-binding proteins (G proteins), which function as modulators or transducers in various transmembrane signaling systems. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes one of the alpha subunits (subunit alpha-11). Mutations in this gene have been associated with hypocalciuric hypercalcemia type II (HHC2) and hypocalcemia dominant 2 (HYPOC2). Patients with HHC2 and HYPOC2 exhibit decreased or increased sensitivity, respectively, to changes in extracellular calcium concentrations. [provided by RefSeq, Dec 2013]

GNA11 Gene-Disease associations (from GenCC):

autosomal dominant hypocalcemia 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
congenital hemangioma
Inheritance: AD Classification: STRONG Submitted by: G2P
familial hypocalciuric hypercalcemia 2
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet
autosomal dominant hypocalcemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GNA11 links:

ENSG00000267139 (HGNC:):

ENSG00000267139 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 19-3119241-C-T is Benign according to our data. Variant chr19-3119241-C-T is described in ClinVar as [Benign]. Clinvar id is 258548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.579 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNA11	NM_002067.5 link	c.771C>T	p.Thr257Thr	synonymous_variant	Exon 6 of 7	ENST00000078429.9	NP_002058.2	P29992

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNA11	ENST00000078429.9 link	c.771C>T	p.Thr257Thr	synonymous_variant	Exon 6 of 7	1	NM_002067.5	ENSP00000078429.3		P29992

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58250

AN:

151846

Hom.:

12137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.413

Gnomad EAS

AF:

0.410

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.368

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.477

Gnomad OTH

AF:

0.395

GnomAD2 exomes

AF:

0.427

AC:

107299

AN:

251156

AF XY:

0.431

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.422

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.407

Gnomad FIN exome

AF:

0.375

Gnomad NFE exome

AF:

0.476

Gnomad OTH exome

AF:

0.436

GnomAD4 exome

AF:

0.465

AC:

679315

AN:

1460394

Hom.:

160274

Cov.:

AF XY:

0.465

AC XY:

337506

AN XY:

726498

show subpopulations

African (AFR)

AF:

0.209

AC:

7001

AN:

33440

American (AMR)

AF:

0.417

AC:

18650

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

10628

AN:

26130

East Asian (EAS)

AF:

0.438

AC:

17368

AN:

39690

South Asian (SAS)

AF:

0.422

AC:

36249

AN:

85938

European-Finnish (FIN)

AF:

0.376

AC:

20037

AN:

53286

Middle Eastern (MID)

AF:

0.436

AC:

2515

AN:

5768

European-Non Finnish (NFE)

AF:

0.486

AC:

539657

AN:

1111100

Other (OTH)

AF:

0.451

AC:

27210

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

18153

36305

54458

72610

90763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.384

AC:

58289

AN:

151964

Hom.:

12144

Cov.:

AF XY:

0.379

AC XY:

28141

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.216

AC:

8944

AN:

41484

American (AMR)

AF:

0.410

AC:

6255

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

1433

AN:

3470

East Asian (EAS)

AF:

0.411

AC:

2118

AN:

5158

South Asian (SAS)

AF:

0.421

AC:

2011

AN:

4772

European-Finnish (FIN)

AF:

0.368

AC:

3894

AN:

10582

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.477

AC:

32414

AN:

67914

Other (OTH)

AF:

0.397

AC:

837

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1752

3504

5257

7009

8761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.429

Hom.:

8134

Bravo

AF:

0.378

Asia WGS

AF:

0.410

AC:

1426

AN:

3478

EpiCase

AF:

0.472

EpiControl

AF:

0.472

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Thr257Thr in exon 6 of GNA11: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 46.79% (31211/66704) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs4900). -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

0.58

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

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rs4900

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