11-124015645-T-C

Variant names:

• chr11-124015645-T-C
• rs547068
• NM_001004462.2:c.71T>C

Variant summary

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

The NM_001004462.2(OR10G4):​c.71T>C​(p.Leu24Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,060 control chromosomes in the GnomAD database, including 5,394 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.24 (5394 hom., cov: 30)
  • Exomes 𝑓: 0.25 (62709 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR10G4 NM_001004462.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.426

Genes affected

OR10G4 (HGNC:14809): (olfactory receptor family 10 subfamily G member 4) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003057152).
• BP6: Variant 11-124015645-T-C is Benign according to our data. Variant chr11-124015645-T-C is described in ClinVar as [Benign]. Clinvar id is 2796335.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10G4	NM_001004462.2	c.71T>C	p.Leu24Pro	missense_variant	Exon 2 of 2	ENST00000641722.1	NP_001004462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR10G4	ENST00000641722.1	c.71T>C	p.Leu24Pro	missense_variant	Exon 2 of 2		NM_001004462.2	ENSP00000493036.1
OR10G4	ENST00000641521.1	c.71T>C	p.Leu24Pro	missense_variant	Exon 3 of 3			ENSP00000493354.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36664 AN: 150944 Hom.: 5395 Cov.: 30

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.228

GnomAD3 exomes AF: 0.126 AC: 26241 AN: 207902 Hom.: 6452 AF XY: 0.120 AC XY: 13481 AN XY: 112474

Gnomad AFR exome AF: 0.0410

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.0604

Gnomad EAS exome AF: 0.245

Gnomad SAS exome AF: 0.0774

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.138

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.249 AC: 313777 AN: 1261048 Hom.: 62709 Cov.: 62 AF XY: 0.243 AC XY: 153323 AN XY: 629876

Gnomad4 AFR exome AF: 0.0550

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.324

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.243 AC: 36684 AN: 151060 Hom.: 5394 Cov.: 30 AF XY: 0.247 AC XY: 18223 AN XY: 73720

Gnomad4 AFR AF: 0.0908

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.229

Alfa AF: 0.223 Hom.: 945

Bravo AF: 0.234

ExAC AF: 0.171 AC: 20682

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 06, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.9
DANN	Benign	0.094
DEOGEN2	Benign	0.0071	T;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.0038	.;.;T
MetaRNN	Benign	0.0031	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.72	N;N;N
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.0	.;.;N
REVEL	Benign	0.047
Sift	Benign	0.55	.;.;T
Sift4G	Benign	0.46	.;.;T
Polyphen		0.0	B;B;B
Vest4		0.062
MPC		0.76
ClinPred		0.0031	T
GERP RS		-2.7
Varity_R		0.20
gMVP		0.57

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: rs547068; hg19: chr11-123886352; COSMIC: COSV57976718;