rs12669805

Positions:

• chr7-80041803-T-C

Variant summary

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

The ENST00000649225.1(GNAI1):​c.-336-37251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,144 control chromosomes in the GnomAD database, including 4,827 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 0.16 (4827 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 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.-336-37251T>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23840 AN: 152026 Hom.: 4815 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0748

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.157 AC: 23894 AN: 152144 Hom.: 4827 Cov.: 32 AF XY: 0.153 AC XY: 11368 AN XY: 74394

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.0747

Gnomad4 ASJ AF: 0.0259

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0522

Gnomad4 FIN AF: 0.0209

Gnomad4 NFE AF: 0.0226

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0744 Hom.: 886

Bravo AF: 0.176

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12669805; hg19: chr7-79671119;