ENST00000649225.1:c.-337+17774A>G

Variant names:

• chr7-79974840-A-G
• rs4731111
• ENST00000649225.1:c.-337+17774A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000649225.1(GNAI1):​c.-337+17774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,098 control chromosomes in the GnomAD database, including 3,113 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 0.20 (3113 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAI1	ENST00000649225.1	c.-337+17774A>G		intron_variant	Intron 3 of 12			ENSP00000496829.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30303 AN: 151980 Hom.: 3110 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.200 AC: 30346 AN: 152098 Hom.: 3113 Cov.: 32 AF XY: 0.198 AC XY: 14705 AN XY: 74336

African (AFR) AF: 0.212 AC: 8779 AN: 41492

American (AMR) AF: 0.220 AC: 3368 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1345 AN: 5166

South Asian (SAS) AF: 0.0785 AC: 379 AN: 4828

European-Finnish (FIN) AF: 0.160 AC: 1686 AN: 10566

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13689 AN: 67978

Other (OTH) AF: 0.186 AC: 393 AN: 2114

Alfa AF: 0.198 Hom.: 11221

Bravo AF: 0.204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.65
PhyloP100		0.71

Splicing

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

Other links and lift over

dbSNP: rs4731111; hg19: chr7-79604156;