11-55603767-C-T

Variant names:

• chr11-55603767-C-T
• rs201559565
• NM_001004700.3:c.607G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004700.3(OR4C11):​c.607G>A​(p.Ala203Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,350,602 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A203S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000015 (1 hom.)
• Consequence: OR4C11 NM_001004700.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.93
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04833311).

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.607G>A	p.Ala203Thr	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.607G>A	p.Ala203Thr	missense	Exon 4 of 4	ENSP00000492971.1	Q6IEV9

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1350602 Hom.: 1 Cov.: 30 AF XY: 0.00000298 AC XY: 2 AN XY: 671982

African (AFR) AF: 0.00 AC: 0 AN: 32860

American (AMR) AF: 0.00 AC: 0 AN: 37228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24338

East Asian (EAS) AF: 0.00 AC: 0 AN: 34550

South Asian (SAS) AF: 0.00 AC: 0 AN: 80560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5026

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1032088

Other (OTH) AF: 0.0000358 AC: 2 AN: 55858

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.43
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.00085	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.61	N
PhyloP100		-2.9
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.050
Sift	Benign	0.36	T
Sift4G	Benign	0.35	T
Polyphen		0.024	B
Vest4		0.085
MutPred		0.15		Loss of glycosylation at S199 (P = 0.2098)
MVP		0.14
MPC		0.0033
ClinPred		0.46	T
GERP RS		1.4
Varity_R		0.055
gMVP		0.067
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs201559565; hg19: chr11-55371243;