chr1-109548649-C-T

Variant names:

• chr1-109548649-C-T
• rs3737182
• NM_006496.4:c.-72C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0100
• Publications: 20 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]

ENSG00000290117 (HGNC:):

GPR61 (HGNC:13300): (G protein-coupled receptor 61) This gene belongs to the G-protein coupled receptor 1 family. G protein-coupled receptors contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins. The protein encoded by this gene is most closely related to biogenic amine receptors. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1274531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAI3	NM_006496.4	MANE Select	c.-72C>T		5_prime_UTR	Exon 1 of 9	NP_006487.1	P08754

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAI3	ENST00000369851.7	TSL:1 MANE Select	c.-72C>T		5_prime_UTR	Exon 1 of 9	ENSP00000358867.4	P08754
	GNAI3	ENST00000920644.1		c.-72C>T		5_prime_UTR	Exon 1 of 9	ENSP00000590703.1
	GNAI3	ENST00000879740.1		c.-72C>T		5_prime_UTR	Exon 1 of 8	ENSP00000549799.1

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

African (AFR) AF: 0.131 AC: 2990 AN: 22852

American (AMR) AF: 0.178 AC: 6934 AN: 38990

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 4881 AN: 20896

East Asian (EAS) AF: 0.343 AC: 12318 AN: 35862

South Asian (SAS) AF: 0.287 AC: 20128 AN: 70038

European-Finnish (FIN) AF: 0.199 AC: 10069 AN: 50480

Middle Eastern (MID) AF: 0.169 AC: 549 AN: 3246

European-Non Finnish (NFE) AF: 0.186 AC: 112376 AN: 604906

Other (OTH) AF: 0.204 AC: 8370 AN: 40972

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

African (AFR) AF: 0.137 AC: 5699 AN: 41520

American (AMR) AF: 0.162 AC: 2474 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 803 AN: 3470

East Asian (EAS) AF: 0.360 AC: 1860 AN: 5160

South Asian (SAS) AF: 0.294 AC: 1420 AN: 4824

European-Finnish (FIN) AF: 0.209 AC: 2208 AN: 10588

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12662 AN: 67978

Other (OTH) AF: 0.182 AC: 383 AN: 2110

Alfa AF: 0.181 Hom.: 426

Bravo AF: 0.176

Asia WGS AF: 0.296 AC: 1027 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.1
DANN	Benign	0.86
PhyloP100		0.010
PromoterAI		-0.052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	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: rs3737182; hg19: chr1-110091271; COSMIC: COSV63983763; COSMIC: COSV63983763;