ENST00000649225.1:c.-433-20208T>C

Variant names:

• chr7-79936762-T-C
• rs6967965
• ENST00000649225.1:c.-433-20208T>C

Variant summary

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

The ENST00000649225.1(GNAI1):​c.-433-20208T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,156 control chromosomes in the GnomAD database, including 2,705 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 0.18 (2705 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 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.-433-20208T>C		intron_variant	Intron 2 of 12			ENSP00000496829.1
GNAI1	ENST00000650351.1	n.383-20208T>C		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27186 AN: 152038 Hom.: 2698 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.179 AC: 27223 AN: 152156 Hom.: 2705 Cov.: 32 AF XY: 0.174 AC XY: 12933 AN XY: 74420

African (AFR) AF: 0.240 AC: 9943 AN: 41496

American (AMR) AF: 0.121 AC: 1850 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0433 AC: 209 AN: 4826

European-Finnish (FIN) AF: 0.149 AC: 1577 AN: 10586

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.188 AC: 12772 AN: 67984

Other (OTH) AF: 0.157 AC: 331 AN: 2112

Alfa AF: 0.178 Hom.: 1340

Bravo AF: 0.177

Asia WGS AF: 0.0420 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.49
PhyloP100		-0.41

Splicing

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

Other links and lift over

dbSNP: rs6967965; hg19: chr7-79566078;