rs6466884

Variant names:

• chr7-79989696-T-C
• rs6466884
• ENST00000649225.1:c.-337+32630T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-79989696-T-C
• chr7-79989696-T-G

Variant summary

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

The ENST00000649225.1(GNAI1):​c.-337+32630T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,956 control chromosomes in the GnomAD database, including 7,278 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 0.26 (7278 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 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+32630T>C		intron_variant	Intron 3 of 12			ENSP00000496829.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39576 AN: 151838 Hom.: 7248 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.261 AC: 39651 AN: 151956 Hom.: 7278 Cov.: 32 AF XY: 0.256 AC XY: 19046 AN XY: 74266

African (AFR) AF: 0.524 AC: 21702 AN: 41408

American (AMR) AF: 0.145 AC: 2213 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3470

East Asian (EAS) AF: 0.168 AC: 870 AN: 5166

South Asian (SAS) AF: 0.0784 AC: 378 AN: 4824

European-Finnish (FIN) AF: 0.173 AC: 1828 AN: 10558

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11681 AN: 67956

Other (OTH) AF: 0.204 AC: 429 AN: 2098

Alfa AF: 0.178 Hom.: 5396

Bravo AF: 0.269

Asia WGS AF: 0.141 AC: 490 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.79
PhyloP100		-0.62

Splicing

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

Other links and lift over

dbSNP: rs6466884; hg19: chr7-79619012;