11-55603767-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001004700.3(OR4C11):​c.607G>T​(p.Ala203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000367 in 1,488,706 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (6 hom., cov: 25)
  • Exomes 𝑓: 0.00038 (119 hom.)
• Consequence: OR4C11 NM_001004700.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.93
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016928613).
• BS2: High Homozygotes in GnomAd4 at 6 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.607G>T	p.Ala203Ser	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>T	p.Ala203Ser	missense	Exon 4 of 4	ENSP00000492971.1	Q6IEV9

Frequencies

GnomAD3 genomes AF: 0.000268 AC: 37 AN: 138014 Hom.: 6 Cov.: 25

Gnomad AFR AF: 0.0000755

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: 0.000531

Gnomad OTH AF: 0.000541

GnomAD2 exomes AF: 0.000445 AC: 101 AN: 226858 AF XY: 0.000333

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: 0.000104

Gnomad NFE exome AF: 0.000921

Gnomad OTH exome AF: 0.000180

GnomAD4 exome AF: 0.000377 AC: 509 AN: 1350604 Hom.: 119 Cov.: 30 AF XY: 0.000318 AC XY: 214 AN XY: 671984

African (AFR) AF: 0.000152 AC: 5 AN: 32860

American (AMR) AF: 0.0000806 AC: 3 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: 0.000291 AC: 14 AN: 48094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5028

European-Non Finnish (NFE) AF: 0.000421 AC: 435 AN: 1032088

Other (OTH) AF: 0.000931 AC: 52 AN: 55858

GnomAD4 genome AF: 0.000268 AC: 37 AN: 138102 Hom.: 6 Cov.: 25 AF XY: 0.000269 AC XY: 18 AN XY: 67020

African (AFR) AF: 0.0000752 AC: 3 AN: 39868

American (AMR) AF: 0.00 AC: 0 AN: 12608

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.000531 AC: 33 AN: 62132

Other (OTH) AF: 0.000541 AC: 1 AN: 1850

Alfa AF: 0.000164 Hom.: 1

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000374 AC: 3

ExAC AF: 0.000793 AC: 90

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	0.13
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.84
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.00080	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-2.9
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.051
Sift	Benign	0.21	T
Sift4G	Benign	0.36	T
Polyphen		0.043	B
Vest4		0.045
MVP		0.13
MPC		0.0036
ClinPred		0.014	T
GERP RS		1.4
Varity_R		0.10
gMVP		0.070
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;