chr7-79844275-A-C

Variant names:

• chr7-79844275-A-C
• rs2707876
• ENST00000649225.1:c.-434+71275A>C

Variant summary

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

The ENST00000649225.1(GNAI1):​c.-434+71275A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 149,758 control chromosomes in the GnomAD database, including 7,214 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 0.28 (7214 hom., cov: 31)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 0 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 (NFE) allele frequency at 95% confidence interval = 0.312 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.-434+71275A>C		intron_variant	Intron 2 of 12			ENSP00000496829.1
GNAI1	ENST00000650351.1	n.281+32437A>C		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42306 AN: 149650 Hom.: 7202 Cov.: 31

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.283 AC: 42344 AN: 149758 Hom.: 7214 Cov.: 31 AF XY: 0.278 AC XY: 20336 AN XY: 73222

African (AFR) AF: 0.282 AC: 11085 AN: 39282

American (AMR) AF: 0.222 AC: 3381 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 903 AN: 3468

East Asian (EAS) AF: 0.147 AC: 760 AN: 5176

South Asian (SAS) AF: 0.197 AC: 952 AN: 4828

European-Finnish (FIN) AF: 0.272 AC: 2865 AN: 10542

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.316 AC: 21458 AN: 67972

Other (OTH) AF: 0.297 AC: 621 AN: 2090

Alfa AF: 0.307 Hom.: 1017

Bravo AF: 0.276

Asia WGS AF: 0.190 AC: 662 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.62
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs2707876; hg19: chr7-79473591;