NM_001004700.3:c.537G>T

Variant names:

• chr11-55603837-C-A
• rs61735721
• NM_001004700.3:c.537G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001004700.3(OR4C11):​c.537G>T​(p.Leu179Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,491,452 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000065 (1 hom., cov: 25)
  • Exomes 𝑓: 0.0000074 (2 hom.)
• Consequence: OR4C11 NM_001004700.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.67
• Publications: 1 publications found

Genes affected

OR4C11 (HGNC:15167): (olfactory receptor family 4 subfamily C member 11) 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.123797536).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004700.3. 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
	OR4C11	NM_001004700.3	MANE Select	c.537G>T	p.Leu179Phe	missense	Exon 4 of 4	NP_001004700.2	Q6IEV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4C11	ENST00000641580.1	MANE Select	c.537G>T	p.Leu179Phe	missense	Exon 4 of 4	ENSP00000492971.1	Q6IEV9

Frequencies

GnomAD3 genomes AF: 0.0000654 AC: 9 AN: 137636 Hom.: 1 Cov.: 25

Gnomad AFR AF: 0.000227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000879 AC: 2 AN: 227460 AF XY: 0.00000811

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.00

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: 0.00

GnomAD4 exome AF: 0.00000739 AC: 10 AN: 1353816 Hom.: 2 Cov.: 30 AF XY: 0.00000594 AC XY: 4 AN XY: 673446

African (AFR) AF: 0.000304 AC: 10 AN: 32898

American (AMR) AF: 0.00 AC: 0 AN: 37258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24380

East Asian (EAS) AF: 0.00 AC: 0 AN: 34564

South Asian (SAS) AF: 0.00 AC: 0 AN: 80614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5034

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1035002

Other (OTH) AF: 0.00 AC: 0 AN: 55948

GnomAD4 genome AF: 0.0000654 AC: 9 AN: 137636 Hom.: 1 Cov.: 25 AF XY: 0.0000300 AC XY: 2 AN XY: 66666

African (AFR) AF: 0.000227 AC: 9 AN: 39676

American (AMR) AF: 0.00 AC: 0 AN: 12504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3198

East Asian (EAS) AF: 0.00 AC: 0 AN: 4182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62062

Other (OTH) AF: 0.00 AC: 0 AN: 1832

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000264 AC: 3

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	0.19
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-2.7
PrimateAI	Benign	0.17	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.087
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.051	T
Polyphen		0.99	D
Vest4		0.052
MutPred		0.47		Gain of methylation at K184 (P = 0.0771)
MVP		0.47
MPC		0.0050
ClinPred		0.72	D
GERP RS		0.073
Varity_R		0.25
gMVP		0.059
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs61735721; hg19: chr11-55371313;