11-4999236-C-T

Variant names:

• chr11-4999236-C-T
• rs757522991
• NM_001004755.2:c.254C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004755.2(OR51L1):​c.254C>T​(p.Ala85Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR51L1 NM_001004755.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530

Genes affected

OR51L1 (HGNC:14759): (olfactory receptor family 51 subfamily L 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05134666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51L1	NM_001004755.2	c.254C>T	p.Ala85Val	missense_variant	Exon 3 of 3	ENST00000641819.1	NP_001004755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR51L1	ENST00000641819.1	c.254C>T	p.Ala85Val	missense_variant	Exon 3 of 3		NM_001004755.2	ENSP00000493015.1
OR51L1	ENST00000641624.1	n.587+1653C>T		intron_variant	Intron 2 of 3
OR51L1	ENST00000642056.1	n.587+1653C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251330 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135824

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.54	.;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.44	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.3	.;N
REVEL	Benign	0.038
Sift	Uncertain	0.029	.;D
Sift4G	Uncertain	0.045	.;D
Polyphen		0.0010	B;B
Vest4		0.10
MutPred		0.44		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.14
MPC		0.033
ClinPred		0.030	T
GERP RS		1.2
Varity_R		0.087
gMVP		0.073

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: rs757522991; hg19: chr11-5020466;