ENST00000649225.1:c.-336-13617G>A

Variant names:

• chr7-80065437-G-A
• rs10486920
• ENST00000649225.1:c.-336-13617G>A

Variant summary

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

The ENST00000649225.1(GNAI1):​c.-336-13617G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,038 control chromosomes in the GnomAD database, including 3,445 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 0.21 (3445 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 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.-336-13617G>A		intron	N/A	ENSP00000496829.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31535 AN: 151920 Hom.: 3438 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.208 AC: 31563 AN: 152038 Hom.: 3445 Cov.: 32 AF XY: 0.206 AC XY: 15324 AN XY: 74300

African (AFR) AF: 0.179 AC: 7413 AN: 41452

American (AMR) AF: 0.170 AC: 2596 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3466

East Asian (EAS) AF: 0.155 AC: 804 AN: 5184

South Asian (SAS) AF: 0.168 AC: 810 AN: 4818

European-Finnish (FIN) AF: 0.221 AC: 2328 AN: 10552

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16314 AN: 67982

Other (OTH) AF: 0.221 AC: 466 AN: 2112

Alfa AF: 0.224 Hom.: 16707

Bravo AF: 0.201

Asia WGS AF: 0.158 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.76
PhyloP100		1.7

Splicing

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

Other links and lift over

dbSNP: rs10486920; hg19: chr7-79694753;