11-4955500-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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

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

Verdict is Benign. Variant got -10 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.
• BS2: High Homozygotes in GnomAdExome at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR51A2	NM_001004748.1	c.214G>A	p.Asp72Asn	missense_variant	1/1	ENST00000380371.1
MMP26	NM_021801.5	c.-144-32568C>T		intron_variant		ENST00000380390.6
MMP26	NM_001384608.1	c.-152-32770C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR51A2	ENST00000380371.1	c.214G>A	p.Asp72Asn	missense_variant	1/1		NM_001004748.1	P1
MMP26	ENST00000380390.6	c.-144-32568C>T		intron_variant		5	NM_021801.5	P1
MMP26	ENST00000300762.2	c.-152-32770C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 865 AN: 117316 Hom.: 10 Cov.: 17 FAILED QC

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

GnomAD3 exomes AF: 0.00481 AC: 997 AN: 207318 Hom.: 20 AF XY: 0.00468 AC XY: 524 AN XY: 111878

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 SAS exome AF: 0.00162

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

Gnomad4 AFR exome AF: 0.00405

Gnomad4 AMR exome AF: 0.00637

Gnomad4 ASJ exome AF: 0.0114

Gnomad4 EAS exome AF: 0.0000816

Gnomad4 SAS exome AF: 0.00321

Gnomad4 FIN exome AF: 0.00977

Gnomad4 NFE exome AF: 0.00821

Gnomad4 OTH exome AF: 0.0106

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

Gnomad4 AFR AF: 0.00391

Gnomad4 AMR AF: 0.00601

Gnomad4 ASJ AF: 0.00976

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00381

Gnomad4 FIN AF: 0.00479

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.00908

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

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
MutationTaster	Benign	1.0	D;D
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
Varity_R		0.50
gMVP		0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs113733838; hg19: chr11-4976730; COSMIC: COSV66748514;