rs17802148

chr7-80007366-T-C

Variant summary

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

The ENST00000649225.1(GNAI1):c.-337+50300T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,144 control chromosomes in the GnomAD database, including 1,031 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 0.11 (1031 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 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+50300T>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16641 AN: 152026 Hom.: 1030 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0870

Gnomad ASJ AF: 0.0783

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.109 AC: 16648 AN: 152144 Hom.: 1031 Cov.: 32 AF XY: 0.108 AC XY: 8029 AN XY: 74362

Gnomad4 AFR AF: 0.0799

Gnomad4 AMR AF: 0.0868

Gnomad4 ASJ AF: 0.0783

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0333

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.112

Alfa AF: 0.127 Hom.: 1771

Bravo AF: 0.103

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.79
Dann	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17802148; hg19: chr7-79636682;