rs1018933

Positions:

• chr7-80117245-C-T

Variant summary

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

The ENST00000648663.1(GNAI1):​c.-378+5867C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,186 control chromosomes in the GnomAD database, including 55,287 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 0.85 (55287 hom., cov: 32)
• Consequence: GNAI1 ENST00000648663.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.885 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	ENST00000648663.1	c.-378+5867C>T		intron_variant				P1
GNAI1	ENST00000649225.1	c.-248-16975C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129516 AN: 152068 Hom.: 55239 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.856

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

GnomAD4 genome AF: 0.852 AC: 129620 AN: 152186 Hom.: 55287 Cov.: 32 AF XY: 0.855 AC XY: 63611 AN XY: 74392

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.907

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.857

Alfa AF: 0.860 Hom.: 37210

Bravo AF: 0.850

Asia WGS AF: 0.882 AC: 3067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1018933; hg19: chr7-79746561; COSMIC: COSV53898813;