chr11-4955092-G-T

Variant names:

• chr11-4955092-G-T
• rs547433825
• NM_001004748.1:c.622C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004748.1(OR51A2):​c.622C>A​(p.Leu208Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. L208V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR51A2 NM_001004748.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -11.1
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.045153707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51A2	NM_001004748.1	c.622C>A	p.Leu208Ile	missense_variant	Exon 1 of 1	ENST00000380371.1	NP_001004748.1
MMP26	NM_021801.5	c.-144-32976G>T		intron_variant	Intron 2 of 7	ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-152-33178G>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.622C>A	p.Leu208Ile	missense_variant	Exon 1 of 1	6	NM_001004748.1	ENSP00000369729.1
MMP26	ENST00000380390.6	c.-144-32976G>T		intron_variant	Intron 2 of 7	5	NM_021801.5	ENSP00000369753.1
MMP26	ENST00000300762.2	c.-152-33178G>T		intron_variant	Intron 2 of 7	1		ENSP00000300762.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 117958 Hom.: 0 Cov.: 17

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: 0.00 AC: 0 AN: 222884 AF XY: 0.00

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: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1308082 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 653040

African (AFR) AF: 0.00 AC: 0 AN: 31958

American (AMR) AF: 0.00 AC: 0 AN: 36664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24330

East Asian (EAS) AF: 0.00 AC: 0 AN: 34302

South Asian (SAS) AF: 0.00 AC: 0 AN: 81808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5486

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 989720

Other (OTH) AF: 0.00 AC: 0 AN: 55014

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 117958 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 56950

African (AFR) AF: 0.00 AC: 0 AN: 35312

American (AMR) AF: 0.00 AC: 0 AN: 10296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2752

East Asian (EAS) AF: 0.00 AC: 0 AN: 3844

South Asian (SAS) AF: 0.00 AC: 0 AN: 3926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52316

Other (OTH) AF: 0.00 AC: 0 AN: 1532

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.0010
DANN	Benign	0.32
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-2.5
Eigen_PC	Benign	-2.7
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.040	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.18	N
PhyloP100		-11
PROVEAN	Benign	0.12	N
REVEL	Benign	0.068
Sift	Benign	0.44	T
Sift4G	Benign	0.36	T
Polyphen		0.060	B
Vest4		0.044
MutPred		0.43		Loss of catalytic residue at L208 (P = 0.0331);
MVP		0.61
MPC		1.2
ClinPred		0.10	T
GERP RS		-6.0
Varity_R		0.049
gMVP		0.046
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs547433825; hg19: chr11-4976322;