Variant chr19-3119186-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002067.5(GNA11):c.736-20T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 1,611,764 control chromosomes in the GnomAD database, including 582,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 51932 hom., cov: 31)

Exomes 𝑓: 0.85 ( 530768 hom. )

Consequence

GNA11
NM_002067.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.805

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-3119186-T-G is Benign according to our data. Variant chr19-3119186-T-G is described in ClinVar as [Benign]. Clinvar id is 258547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3119186-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA11	NM_002067.5 linkuse as main transcript	c.736-20T>G		intron_variant		ENST00000078429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA11	ENST00000078429.9 linkuse as main transcript	c.736-20T>G		intron_variant		1	NM_002067.5	P1
	ENST00000587701.1 linkuse as main transcript	n.51+68A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.824

AC:

125230

AN:

151934

Hom.:

51891

Cov.:

show subpopulations

Gnomad AFR

AF:

0.737

Gnomad AMI

AF:

0.707

Gnomad AMR

AF:

0.883

Gnomad ASJ

AF:

0.853

Gnomad EAS

AF:

0.759

Gnomad SAS

AF:

0.747

Gnomad FIN

AF:

0.873

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.867

Gnomad OTH

AF:

0.840

GnomAD3 exomes

AF:

0.839

AC:

209864

AN:

250074

Hom.:

88611

AF XY:

0.835

AC XY:

112895

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.729

Gnomad AMR exome

AF:

0.906

Gnomad ASJ exome

AF:

0.850

Gnomad EAS exome

AF:

0.762

Gnomad SAS exome

AF:

0.736

Gnomad FIN exome

AF:

0.874

Gnomad NFE exome

AF:

0.867

Gnomad OTH exome

AF:

0.855

GnomAD4 exome

AF:

0.852

AC:

1243235

AN:

1459712

Hom.:

530768

Cov.:

AF XY:

0.849

AC XY:

616424

AN XY:

726100

show subpopulations

Gnomad4 AFR exome

AF:

0.736

Gnomad4 AMR exome

AF:

0.905

Gnomad4 ASJ exome

AF:

0.848

Gnomad4 EAS exome

AF:

0.795

Gnomad4 SAS exome

AF:

0.741

Gnomad4 FIN exome

AF:

0.876

Gnomad4 NFE exome

AF:

0.863

Gnomad4 OTH exome

AF:

0.844

GnomAD4 genome

AF:

0.824

AC:

125330

AN:

152052

Hom.:

51932

Cov.:

AF XY:

0.822

AC XY:

61101

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.737

Gnomad4 AMR

AF:

0.883

Gnomad4 ASJ

AF:

0.853

Gnomad4 EAS

AF:

0.759

Gnomad4 SAS

AF:

0.748

Gnomad4 FIN

AF:

0.873

Gnomad4 NFE

AF:

0.867

Gnomad4 OTH

AF:

0.837

Alfa

AF:

0.843

Hom.:

5926

Bravo

AF:

0.824

Asia WGS

AF:

0.764

AC:

2660

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.16

DANN

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over