7-80106723-T-G

Variant names:

• chr7-80106723-T-G
• rs10248649
• ENST00000648663.1:c.-534+444T>G

Variant summary

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

The ENST00000648663.1(GNAI1):​c.-534+444T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,086 control chromosomes in the GnomAD database, including 52,024 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 0.82 (52024 hom., cov: 32)
• Consequence: GNAI1 ENST00000648663.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408
• 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: G2P, Broad Center for Mendelian Genomics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648663.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAI1	ENST00000648663.1		c.-534+444T>G		intron	N/A	ENSP00000497379.1
	GNAI1	ENST00000649225.1		c.-248-27497T>G		intron	N/A	ENSP00000496829.1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125299 AN: 151968 Hom.: 51992 Cov.: 32

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.824 AC: 125376 AN: 152086 Hom.: 52024 Cov.: 32 AF XY: 0.828 AC XY: 61586 AN XY: 74342

African (AFR) AF: 0.726 AC: 30107 AN: 41464

American (AMR) AF: 0.872 AC: 13318 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3020 AN: 3470

East Asian (EAS) AF: 0.853 AC: 4410 AN: 5170

South Asian (SAS) AF: 0.907 AC: 4375 AN: 4822

European-Finnish (FIN) AF: 0.848 AC: 8972 AN: 10582

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58357 AN: 67986

Other (OTH) AF: 0.834 AC: 1762 AN: 2112

Alfa AF: 0.845 Hom.: 161088

Bravo AF: 0.820

Asia WGS AF: 0.872 AC: 3033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.71
PhyloP100		0.41

Splicing

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

Other links and lift over

dbSNP: rs10248649; hg19: chr7-79736039;