chr19-3110351-T-G

Variant names:

Variant summary

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

The NM_002067.5(GNA11):c.321+18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,592,064 control chromosomes in the GnomAD database, including 164,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11806 hom., cov: 32)

Exomes 𝑓: 0.46 ( 152629 hom. )

Consequence

GNA11
NM_002067.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.24

Publications

10 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:

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=-0.91).

BP6

Variant 19-3110351-T-G is Benign according to our data. Variant chr19-3110351-T-G is described in ClinVar as Benign. ClinVar VariationId is 258546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNA11	NM_002067.5 link	c.321+18T>G		intron_variant	Intron 2 of 6	ENST00000078429.9	NP_002058.2	P29992

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNA11	ENST00000078429.9 link	c.321+18T>G		intron_variant	Intron 2 of 6	1	NM_002067.5	ENSP00000078429.3		P29992
GNA11	ENST00000586763.1 link	n.140-2979T>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57375

AN:

151190

Hom.:

11795

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.375

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.376

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.376

GnomAD2 exomes

AF:

0.417

AC:

102212

AN:

244938

AF XY:

0.420

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.410

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.406

Gnomad FIN exome

AF:

0.382

Gnomad NFE exome

AF:

0.466

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.457

AC:

657747

AN:

1440758

Hom.:

152629

Cov.:

AF XY:

0.455

AC XY:

324903

AN XY:

713850

show subpopulations

African (AFR)

AF:

0.210

AC:

6826

AN:

32562

American (AMR)

AF:

0.405

AC:

17945

AN:

44260

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

9537

AN:

25878

East Asian (EAS)

AF:

0.438

AC:

17168

AN:

39230

South Asian (SAS)

AF:

0.403

AC:

34313

AN:

85048

European-Finnish (FIN)

AF:

0.385

AC:

20344

AN:

52804

Middle Eastern (MID)

AF:

0.375

AC:

2132

AN:

5682

European-Non Finnish (NFE)

AF:

0.478

AC:

523378

AN:

1095968

Other (OTH)

AF:

0.440

AC:

26104

AN:

59326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

16890

33780

50669

67559

84449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15488

30976

46464

61952

77440

<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:

0.379

AC:

57415

AN:

151306

Hom.:

11806

Cov.:

AF XY:

0.375

AC XY:

27756

AN XY:

73956

show subpopulations

African (AFR)

AF:

0.217

AC:

8853

AN:

40876

American (AMR)

AF:

0.402

AC:

6133

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

1300

AN:

3470

East Asian (EAS)

AF:

0.408

AC:

2096

AN:

5140

South Asian (SAS)

AF:

0.398

AC:

1903

AN:

4786

European-Finnish (FIN)

AF:

0.376

AC:

3967

AN:

10558

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.471

AC:

32002

AN:

67914

Other (OTH)

AF:

0.379

AC:

797

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1799

3598

5396

7195

8994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.394

Hom.:

4662

Bravo

AF:

0.370

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 29, 2015

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. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

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

-0.91

CADD

Benign

0.40

(source)

DANN

Benign

0.12

PhyloP100

-3.2

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

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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