1-109577110-C-T

Variant names:

• chr1-109577110-C-T
• rs6537837
• NM_006496.4:c.304-2094C>T

Variant summary

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

The NM_006496.4(GNAI3):​c.304-2094C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 150,706 control chromosomes in the GnomAD database, including 2,681 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 (2681 hom., cov: 29)
• Consequence: GNAI3 NM_006496.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 34 publications found

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]

GNAI3 Gene-Disease associations (from GenCC):

• auriculocondylar syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• auriculocondylar syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAI3	NM_006496.4	c.304-2094C>T		intron_variant	Intron 3 of 8	ENST00000369851.7	NP_006487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAI3	ENST00000369851.7	c.304-2094C>T		intron_variant	Intron 3 of 8	1	NM_006496.4	ENSP00000358867.4

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27613 AN: 150594 Hom.: 2684 Cov.: 29

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.183 AC: 27627 AN: 150706 Hom.: 2681 Cov.: 29 AF XY: 0.186 AC XY: 13688 AN XY: 73474

African (AFR) AF: 0.156 AC: 6389 AN: 41074

American (AMR) AF: 0.168 AC: 2541 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 792 AN: 3464

East Asian (EAS) AF: 0.338 AC: 1734 AN: 5128

South Asian (SAS) AF: 0.302 AC: 1447 AN: 4784

European-Finnish (FIN) AF: 0.195 AC: 1963 AN: 10054

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12099 AN: 67752

Other (OTH) AF: 0.190 AC: 397 AN: 2092

Alfa AF: 0.180 Hom.: 10495

Bravo AF: 0.179

Asia WGS AF: 0.285 AC: 989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.68
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6537837; hg19: chr1-110119732;