1-109548649-C-T

Position:

• chr1-109548649-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006496.4(GNAI3):​c.-72C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,040,390 control chromosomes in the GnomAD database, including 22,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2788 hom., cov: 32)
  • Exomes 𝑓: 0.20 (19407 hom.)
• Consequence: GNAI3 NM_006496.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0100

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 1-109548649-C-T is Benign according to our data. Variant chr1-109548649-C-T is described in ClinVar as [Benign]. Clinvar id is 1274531.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAI3	NM_006496.4	c.-72C>T		5_prime_UTR_variant	1/9	ENST00000369851.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAI3	ENST00000369851.7	c.-72C>T		5_prime_UTR_variant	1/9	1	NM_006496.4	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27809 AN: 152028 Hom.: 2789 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.201 AC: 178615 AN: 888242 Hom.: 19407 Cov.: 12 AF XY: 0.205 AC XY: 93668 AN XY: 457828

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.343

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.183 AC: 27824 AN: 152148 Hom.: 2788 Cov.: 32 AF XY: 0.186 AC XY: 13810 AN XY: 74348

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.182

Alfa AF: 0.182 Hom.: 420

Bravo AF: 0.176

Asia WGS AF: 0.296 AC: 1027 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.1
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs3737182; hg19: chr1-110091271; COSMIC: COSV63983763; COSMIC: COSV63983763;