rs6692804

chr1-109566120-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006496.4(GNAI3):c.119-7617G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,076 control chromosomes in the GnomAD database, including 7,323 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 (7323 hom., cov: 32)
• Consequence: GNAI3 NM_006496.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.920

Genes affected

GNAI3 (HGNC:4387): (G protein subunit alpha i3) Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling pathways. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes an alpha subunit and belongs to the G-alpha family. Mutation in this gene, resulting in a gly40-to-arg substitution, is associated with auriculocondylar syndrome, and shown to affect downstream targets in the G protein-coupled endothelin receptor pathway. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAI3	NM_006496.4	c.119-7617G>A		intron_variant		ENST00000369851.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAI3	ENST00000369851.7	c.119-7617G>A		intron_variant		1	NM_006496.4	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43252 AN: 151958 Hom.: 7304 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.285 AC: 43308 AN: 152076 Hom.: 7323 Cov.: 32 AF XY: 0.286 AC XY: 21237 AN XY: 74356

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.267

Alfa AF: 0.211 Hom.: 3306

Bravo AF: 0.290

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.15
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6692804; hg19: chr1-110108742;