Variant 7-80135283-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_002069.6(GNAI1):c.118+5G>A variant causes a splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000614 in 1,455,376 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 3 hom. )

Consequence

GNAI1
NM_002069.6 splice_region, intron

Scores

Splicing: ADA: 0.9997

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.44

Variant links:

Genes affected

GNAI1 (HGNC:4384): (G protein subunit alpha i1) Guanine nucleotide binding proteins are heterotrimeric signal-transducing molecules consisting of alpha, beta, and gamma subunits. The alpha subunit binds guanine nucleotide, can hydrolyze GTP, and can interact with other proteins. The protein encoded by this gene represents the alpha subunit of an inhibitory complex. The encoded protein is part of a complex that responds to beta-adrenergic signals by inhibiting adenylate cyclase. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

GNAI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 7-80135283-G-A is Benign according to our data. Variant chr7-80135283-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2221257.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-80135283-G-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 93 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAI1	NM_002069.6 link	c.118+5G>A		splice_region_variant, intron_variant		ENST00000649796.2	NP_002060.4	P63096-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAI1	ENST00000649796.2 link	c.118+5G>A		splice_region_variant, intron_variant			NM_002069.6	ENSP00000497260.1		P63096-1

Frequencies

GnomAD3 genomes

AF:

0.000611

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000618

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00105

AC:

AN:

85096

Hom.:

AF XY:

0.00100

AC XY:

AN XY:

46932

show subpopulations

Gnomad AFR exome

AF:

0.000324

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00715

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000415

Gnomad FIN exome

AF:

0.000730

Gnomad NFE exome

AF:

0.000781

Gnomad OTH exome

AF:

0.000966

GnomAD4 exome

AF:

0.000614

AC:

800

AN:

1303158

Hom.:

Cov.:

AF XY:

0.000609

AC XY:

391

AN XY:

641572

show subpopulations

Gnomad4 AFR exome

AF:

0.0000752

Gnomad4 AMR exome

AF:

0.000877

Gnomad4 ASJ exome

AF:

0.00528

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000718

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.000499

Gnomad4 OTH exome

AF:

0.000903

GnomAD4 genome

AF:

0.000611

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.000618

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Benign

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.98

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.21

Position offset: -24

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