rs6949761

Positions:

• chr7-79880047-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000649225.1(GNAI1):​c.-433-76923C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,022 control chromosomes in the GnomAD database, including 3,501 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3501 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAI1	ENST00000649225.1	c.-433-76923C>T		intron_variant				ENSP00000496829	P1
GNAI1	ENST00000650351.1	n.282-35020C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31026 AN: 151904 Hom.: 3489 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.188

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.204 AC: 31058 AN: 152022 Hom.: 3501 Cov.: 32 AF XY: 0.201 AC XY: 14900 AN XY: 74304

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.186

Alfa AF: 0.198 Hom.: 534

Bravo AF: 0.204

Asia WGS AF: 0.158 AC: 550 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6949761; hg19: chr7-79509363;