ENST00000649225.1:c.-433-76923C>T

Variant names:

• chr7-79880047-C-T
• rs6949761
• ENST00000649225.1:c.-433-76923C>T

Variant summary

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

The ENST00000649225.1(GNAI1):​c.-433-76923C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,022 control chromosomes in the GnomAD database, including 3,501 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 (3501 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 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.-433-76923C>T		intron	N/A	ENSP00000496829.1
	GNAI1	ENST00000650351.1		n.282-35020C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31026 AN: 151904 Hom.: 3489 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.204 AC: 31058 AN: 152022 Hom.: 3501 Cov.: 32 AF XY: 0.201 AC XY: 14900 AN XY: 74304

African (AFR) AF: 0.296 AC: 12272 AN: 41460

American (AMR) AF: 0.135 AC: 2054 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3468

East Asian (EAS) AF: 0.140 AC: 722 AN: 5164

South Asian (SAS) AF: 0.125 AC: 603 AN: 4816

European-Finnish (FIN) AF: 0.151 AC: 1593 AN: 10566

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12865 AN: 67960

Other (OTH) AF: 0.186 AC: 393 AN: 2116

Alfa AF: 0.200 Hom.: 566

Bravo AF: 0.204

Asia WGS AF: 0.158 AC: 550 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		0.092

Splicing

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

Other links and lift over

dbSNP: rs6949761; hg19: chr7-79509363;