NM_001004748.1:c.214G>A

Variant names:

• chr11-4955500-C-T
• rs113733838
• NM_001004748.1:c.214G>A

Variant summary

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

The NM_001004748.1(OR51A2):​c.214G>A​(p.Asp72Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0074 (10 hom., cov: 17)
  • Exomes 𝑓: 0.0077 (260 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR51A2 NM_001004748.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.38
• Publications: 7 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019027114).
• BP6: Variant 11-4955500-C-T is Benign according to our data. Variant chr11-4955500-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2641537.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51A2	NM_001004748.1	c.214G>A	p.Asp72Asn	missense_variant	Exon 1 of 1	ENST00000380371.1	NP_001004748.1
MMP26	NM_021801.5	c.-144-32568C>T		intron_variant	Intron 2 of 7	ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-152-32770C>T		intron_variant	Intron 2 of 7		NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR51A2	ENST00000380371.1	c.214G>A	p.Asp72Asn	missense_variant	Exon 1 of 1	6	NM_001004748.1	ENSP00000369729.1
MMP26	ENST00000380390.6	c.-144-32568C>T		intron_variant	Intron 2 of 7	5	NM_021801.5	ENSP00000369753.1
MMP26	ENST00000300762.2	c.-152-32770C>T		intron_variant	Intron 2 of 7	1		ENSP00000300762.2

Frequencies

GnomAD3 genomes AF: 0.00737 AC: 865 AN: 117316 Hom.: 10 Cov.: 17

Gnomad AFR AF: 0.00396

Gnomad AMI AF: 0.00704

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.00976

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00381

Gnomad FIN AF: 0.00479

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00917

GnomAD2 exomes AF: 0.00481 AC: 997 AN: 207318 AF XY: 0.00468

Gnomad AFR exome AF: 0.00228

Gnomad AMR exome AF: 0.00487

Gnomad ASJ exome AF: 0.00487

Gnomad EAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00569

Gnomad NFE exome AF: 0.00664

Gnomad OTH exome AF: 0.00731

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00770 AC: 8974 AN: 1166182 Hom.: 260 Cov.: 31 AF XY: 0.00771 AC XY: 4515 AN XY: 585444

African (AFR) AF: 0.00405 AC: 119 AN: 29390

American (AMR) AF: 0.00637 AC: 238 AN: 37380

Ashkenazi Jewish (ASJ) AF: 0.0114 AC: 255 AN: 22306

East Asian (EAS) AF: 0.0000816 AC: 3 AN: 36762

South Asian (SAS) AF: 0.00321 AC: 257 AN: 80128

European-Finnish (FIN) AF: 0.00977 AC: 473 AN: 48430

Middle Eastern (MID) AF: 0.0139 AC: 63 AN: 4536

European-Non Finnish (NFE) AF: 0.00821 AC: 7034 AN: 856836

Other (OTH) AF: 0.0106 AC: 532 AN: 50414

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00736 AC: 864 AN: 117432 Hom.: 10 Cov.: 17 AF XY: 0.00682 AC XY: 388 AN XY: 56932

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00391 AC: 134 AN: 34242

American (AMR) AF: 0.00601 AC: 66 AN: 10984

Ashkenazi Jewish (ASJ) AF: 0.00976 AC: 26 AN: 2664

East Asian (EAS) AF: 0.00 AC: 0 AN: 3776

South Asian (SAS) AF: 0.00381 AC: 15 AN: 3940

European-Finnish (FIN) AF: 0.00479 AC: 36 AN: 7510

Middle Eastern (MID) AF: 0.0208 AC: 5 AN: 240

European-Non Finnish (NFE) AF: 0.0109 AC: 563 AN: 51824

Other (OTH) AF: 0.00908 AC: 14 AN: 1542

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0182 Hom.: 15

ESP6500AA AF: 0.00259 AC: 11

ESP6500EA AF: 0.00879 AC: 72

ExAC AF: 0.00636 AC: 741

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

OR51A2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		3.4
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.38
MVP		0.69
MPC		2.0
ClinPred		0.046	T
GERP RS		2.7
PromoterAI		-0.012	Neutral
Varity_R		0.50
gMVP		0.68
Mutation Taster		=81/19	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: rs113733838; hg19: chr11-4976730; COSMIC: COSV66748514;