7-80213989-C-T

Position:

• chr7-80213989-C-T

Variant summary

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

The NM_002069.6(GNAI1):​c.874+1120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,904 control chromosomes in the GnomAD database, including 7,187 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 0.29 (7187 hom., cov: 31)
• Consequence: GNAI1 NM_002069.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAI1	NM_002069.6	c.874+1120C>T		intron_variant		ENST00000649796.2	NP_002060.4
GNAI1	NM_001256414.2	c.718+1120C>T		intron_variant			NP_001243343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAI1	ENST00000649796.2	c.874+1120C>T		intron_variant			NM_002069.6	ENSP00000497260.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43275 AN: 151786 Hom.: 7182 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.285 AC: 43304 AN: 151904 Hom.: 7187 Cov.: 31 AF XY: 0.282 AC XY: 20923 AN XY: 74252

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.252

Alfa AF: 0.234 Hom.: 8839

Bravo AF: 0.294

Asia WGS AF: 0.130 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2886611; hg19: chr7-79843305;