1-247451233-C-T

Variant names:

• chr1-247451233-C-T
• NM_001004492.2:c.750G>A

Variant summary

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

The NM_001004492.2(OR2B11):​c.750G>A​(p.Met250Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,130 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OR2B11 NM_001004492.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.08

Genes affected

OR2B11 (HGNC:31249): (olfactory receptor family 2 subfamily B member 11) 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=0.034894705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2B11	NM_001004492.2	c.750G>A	p.Met250Ile	missense_variant	Exon 2 of 2	ENST00000641149.2	NP_001004492.1
OR2B11	NR_169840.1	n.1404G>A		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2B11	ENST00000641149.2	c.750G>A	p.Met250Ile	missense_variant	Exon 2 of 2		NM_001004492.2	ENSP00000492892.1
OR2B11	ENST00000641527.1	c.750G>A	p.Met250Ile	missense_variant	Exon 3 of 3			ENSP00000493421.1
OR2B11	ENST00000641613.1	n.1404G>A		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450130 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 719210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.11
DANN	Benign	0.72
DEOGEN2	Benign	0.0012	T;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.71	.;.;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.035	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.60	N;N;N
PrimateAI	Benign	0.18	T
PROVEAN	Benign	0.48	.;.;N
REVEL	Benign	0.058
Sift	Benign	1.0	.;.;T
Sift4G	Benign	0.80	.;.;T
Polyphen		0.0	B;B;B
Vest4		0.061
MutPred		0.22		Loss of sheet (P = 0.3635);Loss of sheet (P = 0.3635);Loss of sheet (P = 0.3635);
MVP		0.27
MPC		0.094
ClinPred		0.054	T
GERP RS		0.86
Varity_R		0.12
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-247614535; COSMIC: COSV104629259; COSMIC: COSV104629259;