chr7-80011397-A-G

Position:

• chr7-80011397-A-G

Variant summary

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

The ENST00000649225.1(GNAI1):​c.-337+54331A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,150 control chromosomes in the GnomAD database, including 1,692 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 0.15 (1692 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 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.-337+54331A>G		intron_variant				ENSP00000496829	P1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22232 AN: 152032 Hom.: 1688 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0941

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0755

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.146 AC: 22250 AN: 152150 Hom.: 1692 Cov.: 32 AF XY: 0.145 AC XY: 10785 AN XY: 74370

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0941

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.0756

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.146

Alfa AF: 0.156 Hom.: 911

Bravo AF: 0.142

Asia WGS AF: 0.113 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7805663; hg19: chr7-79640713;