rs17802148

Variant names:

• chr7-80007366-T-C
• rs17802148
• ENST00000649225.1:c.-337+50300T>C

Variant summary

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

The ENST00000649225.1(GNAI1):​c.-337+50300T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,144 control chromosomes in the GnomAD database, including 1,031 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 0.11 (1031 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAI1	ENST00000649225.1		c.-337+50300T>C		intron	N/A	ENSP00000496829.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16641 AN: 152026 Hom.: 1030 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0870

Gnomad ASJ AF: 0.0783

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.109 AC: 16648 AN: 152144 Hom.: 1031 Cov.: 32 AF XY: 0.108 AC XY: 8029 AN XY: 74362

African (AFR) AF: 0.0799 AC: 3318 AN: 41514

American (AMR) AF: 0.0868 AC: 1325 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0783 AC: 272 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.0333 AC: 161 AN: 4830

European-Finnish (FIN) AF: 0.135 AC: 1433 AN: 10588

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9762 AN: 67986

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.125 Hom.: 2163

Bravo AF: 0.103

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.79
DANN	Benign	0.33
PhyloP100		-0.043

Splicing

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

Other links and lift over

dbSNP: rs17802148; hg19: chr7-79636682;