7-80101245-C-T

Variant names:

• chr7-80101245-C-T
• rs2886607
• ENST00000649225.1:c.-249+22104C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000649225.1(GNAI1):​c.-249+22104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,192 control chromosomes in the GnomAD database, including 58,607 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 0.88 (58607 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976
• Publications: 2 publications found

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]

GNAI1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Broad Center for Mendelian Genomics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000649225.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAI1	ENST00000649225.1		c.-249+22104C>T		intron	N/A	ENSP00000496829.1	P63096-1

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133290 AN: 152074 Hom.: 58555 Cov.: 32

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.882

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

GnomAD4 genome AF: 0.877 AC: 133398 AN: 152192 Hom.: 58607 Cov.: 32 AF XY: 0.881 AC XY: 65540 AN XY: 74404

African (AFR) AF: 0.838 AC: 34783 AN: 41498

American (AMR) AF: 0.900 AC: 13767 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3075 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5162 AN: 5178

South Asian (SAS) AF: 0.949 AC: 4582 AN: 4830

European-Finnish (FIN) AF: 0.882 AC: 9338 AN: 10584

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.879 AC: 59759 AN: 68020

Other (OTH) AF: 0.883 AC: 1868 AN: 2116

Alfa AF: 0.880 Hom.: 29809

Bravo AF: 0.874

Asia WGS AF: 0.965 AC: 3357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.50
DANN	Benign	0.53
PhyloP100		-0.98

Splicing

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

Other links and lift over

dbSNP: rs2886607; hg19: chr7-79730561;