11-55572219-G-T

Variant names:

• chr11-55572219-G-T
• rs374191202
• NM_001004701.2:c.92G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001004701.2(OR4C16):​c.92G>T​(p.Arg31Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000441 in 1,610,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R31C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: OR4C16 NM_001004701.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.360
• Publications: 13 publications found

Genes affected

OR4C16 (HGNC:15172): (olfactory receptor family 4 subfamily C member 16) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016615927).
• BP6: Variant 11-55572219-G-T is Benign according to our data. Variant chr11-55572219-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2383008.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4C16	NM_001004701.2	c.92G>T	p.Arg31Leu	missense_variant	Exon 1 of 1	ENST00000623907.1	NP_001004701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4C16	ENST00000623907.1	c.92G>T	p.Arg31Leu	missense_variant	Exon 1 of 1	6	NM_001004701.2	ENSP00000485295.1

Frequencies

GnomAD3 genomes AF: 0.000231 AC: 35 AN: 151606 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000751

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: 0.0000147

Gnomad OTH AF: 0.00145

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251180 AF XY: 0.0000516

Gnomad AFR exome AF: 0.000615

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: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000240 AC: 35 AN: 1458654 Hom.: 0 Cov.: 33 AF XY: 0.0000207 AC XY: 15 AN XY: 725876

African (AFR) AF: 0.000718 AC: 24 AN: 33436

American (AMR) AF: 0.0000224 AC: 1 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5760

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1109092

Other (OTH) AF: 0.0000166 AC: 1 AN: 60304

GnomAD4 genome AF: 0.000237 AC: 36 AN: 151722 Hom.: 0 Cov.: 31 AF XY: 0.000229 AC XY: 17 AN XY: 74122

African (AFR) AF: 0.000773 AC: 32 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67942

Other (OTH) AF: 0.00143 AC: 3 AN: 2096

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.000276

ESP6500AA AF: 0.000682 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000576 AC: 7

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 14, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.28
DANN	Benign	0.16
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-3.5	N
PhyloP100		0.36
PrimateAI	Benign	0.20	T
Polyphen		0.0	B
ClinPred		0.012	T
GERP RS		3.9
PromoterAI		-0.0062	Neutral
Varity_R		0.057
gMVP		0.12
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs374191202; hg19: chr11-55339695; COSMIC: COSV58942822;