rs4731111

Positions:

• chr7-79974840-A-G
• chr7-79974840-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000649225.1(GNAI1):​c.-337+17774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,098 control chromosomes in the GnomAD database, including 3,113 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 (3113 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAI1	ENST00000649225.1	c.-337+17774A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30303 AN: 151980 Hom.: 3110 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.200 AC: 30346 AN: 152098 Hom.: 3113 Cov.: 32 AF XY: 0.198 AC XY: 14705 AN XY: 74336

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.0785

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.186

Alfa AF: 0.189 Hom.: 4390

Bravo AF: 0.204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4731111; hg19: chr7-79604156;