NM_006496.4:c.119-7617G>A

Variant names:

• chr1-109566120-G-A
• rs6692804
• NM_006496.4:c.119-7617G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006496.4. 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
	GNAI3	NM_006496.4	MANE Select	c.119-7617G>A		intron	N/A	NP_006487.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAI3	ENST00000369851.7	TSL:1 MANE Select	c.119-7617G>A		intron	N/A	ENSP00000358867.4
	GNAI3	ENST00000920644.1		c.119-7617G>A		intron	N/A	ENSP00000590703.1
	GNAI3	ENST00000879740.1		c.119-7617G>A		intron	N/A	ENSP00000549799.1

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

African (AFR) AF: 0.466 AC: 19311 AN: 41448

American (AMR) AF: 0.209 AC: 3198 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 897 AN: 3472

East Asian (EAS) AF: 0.362 AC: 1872 AN: 5172

South Asian (SAS) AF: 0.360 AC: 1739 AN: 4824

European-Finnish (FIN) AF: 0.210 AC: 2223 AN: 10578

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13171 AN: 67990

Other (OTH) AF: 0.267 AC: 564 AN: 2114

Alfa AF: 0.222 Hom.: 5080

Bravo AF: 0.290

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.30
PhyloP100		-0.92
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: rs6692804; hg19: chr1-110108742;