rs1462983

Positions:

• chr11-6108607-C-G
• chr11-6108607-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001005181.2(OR56B4):​c.829C>G​(p.Pro277Ala) 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. 12/21 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. P277S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: OR56B4 NM_001005181.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543

Genes affected

OR56B4 (HGNC:15248): (olfactory receptor family 56 subfamily B member 4) 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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27966595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR56B4	NM_001005181.2	c.829C>G	p.Pro277Ala	missense_variant	1/1	ENST00000316529.3	NP_001005181.1
LOC124902622	XR_007062565.1	n.194+1657G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR56B4	ENST00000316529.3	c.829C>G	p.Pro277Ala	missense_variant	1/1		NM_001005181.2	ENSP00000321196	P1
	ENST00000529961.1	n.372-28G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T
Eigen	Benign	0.053
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.12
Sift	Benign	0.14	T
Sift4G	Benign	0.58	T
Polyphen		1.0	D
Vest4		0.19
MutPred		0.37		Loss of methylation at K272 (P = 0.0905);
MVP		0.45
MPC		0.037
ClinPred		0.83	D
GERP RS		4.0
Varity_R		0.14
gMVP		0.081

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: rs1462983; hg19: chr11-6129837;