11-55603764-T-C

Variant names:

• chr11-55603764-T-C
• rs774932514
• NM_001004700.3:c.610A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001004700.3(OR4C11):​c.610A>G​(p.Ile204Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,351,812 control chromosomes in the GnomAD database, including 4 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.000010 (4 hom.)
• Consequence: OR4C11 NM_001004700.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.33
• 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=0.093933016).
• BP6: Variant 11-55603764-T-C is Benign according to our data. Variant chr11-55603764-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3205425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 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.610A>G	p.Ile204Val	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.610A>G	p.Ile204Val	missense	Exon 4 of 4	ENSP00000492971.1	Q6IEV9

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.0000352 AC: 8 AN: 227084 AF XY: 0.0000406

Gnomad AFR exome AF: 0.00

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: 0.0000104 AC: 14 AN: 1351812 Hom.: 4 Cov.: 30 AF XY: 0.0000104 AC XY: 7 AN XY: 672574

African (AFR) AF: 0.00 AC: 0 AN: 32872

American (AMR) AF: 0.00 AC: 0 AN: 37266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24382

East Asian (EAS) AF: 0.00 AC: 0 AN: 34560

South Asian (SAS) AF: 0.000149 AC: 12 AN: 80596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5032

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1033110

Other (OTH) AF: 0.0000358 AC: 2 AN: 55888

GnomAD4 genome Cov.: 25

ExAC AF: 0.0000264 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.088
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.3
DANN	Benign	0.30
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.00035	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.78	N
PhyloP100		-3.3
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.027
Sift	Benign	0.043	D
Sift4G	Benign	0.070	T
Polyphen		0.019	B
Vest4		0.013
MutPred		0.33		Gain of glycosylation at S199 (P = 0.1109)
MVP		0.061
MPC		0.0036
ClinPred		0.039	T
GERP RS		-3.3
Varity_R		0.069
gMVP		0.055
Mutation Taster		=100/0	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: rs774932514; hg19: chr11-55371240;