rs6967965

Positions:

• chr7-79936762-T-C

Variant summary

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

The ENST00000649225.1(GNAI1):​c.-433-20208T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,156 control chromosomes in the GnomAD database, including 2,705 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 0.18 (2705 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 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.-433-20208T>C		intron_variant				ENSP00000496829	P1
GNAI1	ENST00000650351.1	n.383-20208T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27186 AN: 152038 Hom.: 2698 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.179 AC: 27223 AN: 152156 Hom.: 2705 Cov.: 32 AF XY: 0.174 AC XY: 12933 AN XY: 74420

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0433

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.157

Alfa AF: 0.177 Hom.: 1197

Bravo AF: 0.177

Asia WGS AF: 0.0420 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6967965; hg19: chr7-79566078;