NM_001004752.2:c.815G>A

Variant names:

• chr11-4769124-C-T
• rs201118576
• NM_001004752.2:c.815G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001004752.2(OR51F1):​c.815G>A​(p.Arg272His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000566 in 1,607,916 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000054 (0 hom.)
• Consequence: OR51F1 NM_001004752.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.790
• Publications: 2 publications found

Genes affected

OR51F1 (HGNC:15196): (olfactory receptor family 51 subfamily F member 1) 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]

MMP26 (HGNC:14249): (matrix metallopeptidase 26) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers. [provided by RefSeq, May 2016]

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=0.08727884).
• BP6: Variant 11-4769124-C-T is Benign according to our data. Variant chr11-4769124-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2601304.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51F1	NM_001004752.2	c.815G>A	p.Arg272His	missense_variant	Exon 1 of 1	ENST00000624103.2	NP_001004752.2
MMP26	NM_021801.5	c.-145+1783C>T		intron_variant	Intron 2 of 7	ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-153+1783C>T		intron_variant	Intron 2 of 7		NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR51F1	ENST00000624103.2	c.815G>A	p.Arg272His	missense_variant	Exon 1 of 1	6	NM_001004752.2	ENSP00000485387.2
MMP26	ENST00000380390.6	c.-145+1783C>T		intron_variant	Intron 2 of 7	5	NM_021801.5	ENSP00000369753.1
MMP26	ENST00000300762.2	c.-153+1783C>T		intron_variant	Intron 2 of 7	1		ENSP00000300762.2

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00202

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: 0.000478

GnomAD2 exomes AF: 0.0000650 AC: 16 AN: 246010 AF XY: 0.0000603

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000873

Gnomad ASJ exome AF: 0.00140

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: 0.0000543 AC: 79 AN: 1455800 Hom.: 0 Cov.: 33 AF XY: 0.0000525 AC XY: 38 AN XY: 723730

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.0000899 AC: 4 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.000946 AC: 24 AN: 25378

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.000118 AC: 10 AN: 84980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.0000334 AC: 37 AN: 1108898

Other (OTH) AF: 0.0000665 AC: 4 AN: 60150

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74300

African (AFR) AF: 0.0000724 AC: 3 AN: 41414

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.0000829 Hom.: 0

Bravo AF: 0.0000945

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000412 AC: 5

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 22, 2023

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	0.086
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.0094	.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.3	.;M
PhyloP100		-0.79
PrimateAI	Benign	0.17	T
PROVEAN	Uncertain	-4.4	.;D
REVEL	Benign	0.12
Sift	Uncertain	0.011	.;D
Polyphen		0.86	.;P
Vest4		0.14
MVP		0.41
ClinPred		0.47	T
GERP RS		1.4
Varity_R		0.26
gMVP		0.14
Mutation Taster		=99/1	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: rs201118576; hg19: chr11-4790354; COSMIC: COSV100598678;