rs763306729

Variant names:

• chr11-59477460-G-A
• rs763306729
• NM_001004705.2:c.31G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-59477460-G-A
• chr11-59477460-G-C
• chr11-59477460-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004705.2(OR4D10):​c.31G>A​(p.Glu11Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000668 in 1,587,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: OR4D10 NM_001004705.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12
• Publications: 2 publications found

Genes affected

OR4D10 (HGNC:15173): (olfactory receptor family 4 subfamily D member 10) 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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04663974).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004705.2. 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
	OR4D10	NM_001004705.2	MANE Select	c.31G>A	p.Glu11Lys	missense	Exon 3 of 3	NP_001004705.1	A0A126GVJ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4D10	ENST00000530162.2	TSL:6 MANE Select	c.31G>A	p.Glu11Lys	missense	Exon 3 of 3	ENSP00000436424.1	Q8NGI6

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000361 AC: 83 AN: 229796 AF XY: 0.000282

Gnomad AFR exome AF: 0.0000658

Gnomad AMR exome AF: 0.00264

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000182

GnomAD4 exome AF: 0.0000641 AC: 92 AN: 1435584 Hom.: 0 Cov.: 31 AF XY: 0.0000534 AC XY: 38 AN XY: 711558

African (AFR) AF: 0.0000308 AC: 1 AN: 32416

American (AMR) AF: 0.00222 AC: 90 AN: 40508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24606

East Asian (EAS) AF: 0.00 AC: 0 AN: 39440

South Asian (SAS) AF: 0.00 AC: 0 AN: 81870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099284

Other (OTH) AF: 0.0000169 AC: 1 AN: 59194

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.000850 AC: 13 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000107 Hom.: 0

Bravo AF: 0.000215

ExAC AF: 0.000199 AC: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		2.1
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.14
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.024	D
Polyphen		0.20	B
Vest4		0.49
MutPred		0.62		Gain of methylation at E11 (P = 0.0028)
MVP		0.37
MPC		0.017
ClinPred		0.067	T
GERP RS		3.1
Varity_R		0.11
gMVP		0.22
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs763306729; hg19: chr11-59244933;