chr7-80069738-A-G

Variant names:

• chr7-80069738-A-G
• rs10486922
• ENST00000649225.1:c.-336-9316A>G

Variant summary

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

The ENST00000649225.1(GNAI1):​c.-336-9316A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,068 control chromosomes in the GnomAD database, including 30,803 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 0.61 (30803 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 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.-336-9316A>G		intron_variant	Intron 3 of 12			ENSP00000496829.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93339 AN: 151950 Hom.: 30755 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.614 AC: 93438 AN: 152068 Hom.: 30803 Cov.: 32 AF XY: 0.605 AC XY: 44932 AN XY: 74310

African (AFR) AF: 0.873 AC: 36240 AN: 41502

American (AMR) AF: 0.525 AC: 8013 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1870 AN: 3468

East Asian (EAS) AF: 0.496 AC: 2563 AN: 5170

South Asian (SAS) AF: 0.452 AC: 2175 AN: 4814

European-Finnish (FIN) AF: 0.444 AC: 4689 AN: 10552

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35979 AN: 67974

Other (OTH) AF: 0.593 AC: 1249 AN: 2108

Alfa AF: 0.542 Hom.: 2341

Bravo AF: 0.634

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.48
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs10486922; hg19: chr7-79699054;