11-4954974-C-A

Variant names:

• chr11-4954974-C-A
• rs752232056
• NM_001004748.1:c.740G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001004748.1(OR51A2):​c.740G>T​(p.Cys247Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts 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. C247Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 18)
  • Exomes 𝑓: 0.0000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR51A2 NM_001004748.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 4 publications found

Genes affected

OR51A2 (HGNC:14764): (olfactory receptor family 51 subfamily A member 2) 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]

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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36590686).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004748.1. 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
	OR51A2	NM_001004748.1	MANE Select	c.740G>T	p.Cys247Phe	missense	Exon 1 of 1	NP_001004748.1	Q8NGJ7
	MMP26	NM_021801.5	MANE Select	c.-144-33094C>A		intron	N/A	NP_068573.2	Q9NRE1
	MMP26	NM_001384608.1		c.-152-33296C>A		intron	N/A	NP_001371537.1	A0A8J8YUH5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR51A2	ENST00000380371.1	TSL:6 MANE Select	c.740G>T	p.Cys247Phe	missense	Exon 1 of 1	ENSP00000369729.1	Q8NGJ7
	MMP26	ENST00000380390.6	TSL:5 MANE Select	c.-144-33094C>A		intron	N/A	ENSP00000369753.1	Q9NRE1
	MMP26	ENST00000300762.2	TSL:1	c.-152-33296C>A		intron	N/A	ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 116792 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000467 AC: 1 AN: 214300 AF XY: 0.00000862

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000161 AC: 2 AN: 1242398 Hom.: 0 Cov.: 32 AF XY: 0.00000322 AC XY: 2 AN XY: 621538

African (AFR) AF: 0.00 AC: 0 AN: 31348

American (AMR) AF: 0.00 AC: 0 AN: 35422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23260

East Asian (EAS) AF: 0.00 AC: 0 AN: 34396

South Asian (SAS) AF: 0.0000248 AC: 2 AN: 80716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5168

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 932398

Other (OTH) AF: 0.00 AC: 0 AN: 52730

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 116906 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 56430

African (AFR) AF: 0.00 AC: 0 AN: 35412

American (AMR) AF: 0.00 AC: 0 AN: 10396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2692

East Asian (EAS) AF: 0.00 AC: 0 AN: 4002

South Asian (SAS) AF: 0.00 AC: 0 AN: 4018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51158

Other (OTH) AF: 0.00 AC: 0 AN: 1540

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000916 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.096
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.17
Sift	Benign	0.068	T
Sift4G	Uncertain	0.036	D
Polyphen		0.73	P
Vest4		0.42
MutPred		0.46		Gain of catalytic residue at C242 (P = 0.1303)
MVP		0.70
MPC		2.1
ClinPred		0.54	D
GERP RS		3.3
Varity_R		0.46
gMVP		0.095
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs752232056; hg19: chr11-4976204; COSMIC: COSV100985030;