11-6108607-C-T

Variant names:

• chr11-6108607-C-T
• rs1462983
• NM_001005181.2:c.829C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005181.2(OR56B4):​c.829C>T​(p.Pro277Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,613,382 control chromosomes in the GnomAD database, including 189,522 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.41 (14926 hom., cov: 31)
  • Exomes 𝑓: 0.48 (174596 hom.)
• Consequence: OR56B4 NM_001005181.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• Publications: 30 publications found

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]

ENSG00000254444 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1795751E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005181.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR56B4	NM_001005181.2	MANE Select	c.829C>T	p.Pro277Ser	missense	Exon 1 of 1	NP_001005181.1	Q8NH76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR56B4	ENST00000316529.3	TSL:6 MANE Select	c.829C>T	p.Pro277Ser	missense	Exon 1 of 1	ENSP00000321196.2	Q8NH76
	ENSG00000254444	ENST00000529961.1	TSL:5	n.372-28G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61903 AN: 151824 Hom.: 14922 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.432

GnomAD2 exomes AF: 0.523 AC: 131395 AN: 251468 AF XY: 0.522

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.706

Gnomad ASJ exome AF: 0.480

Gnomad EAS exome AF: 0.852

Gnomad FIN exome AF: 0.493

Gnomad NFE exome AF: 0.453

Gnomad OTH exome AF: 0.518

GnomAD4 exome AF: 0.478 AC: 698392 AN: 1461440 Hom.: 174596 Cov.: 46 AF XY: 0.482 AC XY: 350480 AN XY: 727046

African (AFR) AF: 0.152 AC: 5105 AN: 33476

American (AMR) AF: 0.689 AC: 30799 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 12571 AN: 26134

East Asian (EAS) AF: 0.856 AC: 33985 AN: 39700

South Asian (SAS) AF: 0.600 AC: 51772 AN: 86250

European-Finnish (FIN) AF: 0.495 AC: 26450 AN: 53418

Middle Eastern (MID) AF: 0.461 AC: 2658 AN: 5768

European-Non Finnish (NFE) AF: 0.455 AC: 505799 AN: 1111598

Other (OTH) AF: 0.485 AC: 29253 AN: 60374

GnomAD4 genome AF: 0.407 AC: 61915 AN: 151942 Hom.: 14926 Cov.: 31 AF XY: 0.420 AC XY: 31179 AN XY: 74246

African (AFR) AF: 0.163 AC: 6770 AN: 41466

American (AMR) AF: 0.570 AC: 8705 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1674 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4460 AN: 5152

South Asian (SAS) AF: 0.624 AC: 2994 AN: 4800

European-Finnish (FIN) AF: 0.501 AC: 5285 AN: 10540

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.451 AC: 30645 AN: 67938

Other (OTH) AF: 0.434 AC: 915 AN: 2110

Alfa AF: 0.451 Hom.: 72368

Bravo AF: 0.404

ESP6500AA AF: 0.172 AC: 756

ESP6500EA AF: 0.453 AC: 3891

ExAC AF: 0.508 AC: 61632

Asia WGS AF: 0.691 AC: 2402 AN: 3478

EpiCase AF: 0.457

EpiControl AF: 0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.021
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		-0.54
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.12
Sift	Benign	0.072	T
Sift4G	Benign	0.36	T
Polyphen		1.0	D
Vest4		0.016
MPC		0.020
ClinPred		0.071	T
GERP RS		4.0
Varity_R		0.14
gMVP		0.15
Mutation Taster		=100/0	polymorphism (auto)

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: rs1462983; hg19: chr11-6129837; COSMIC: COSV57205164;