11-6108607-C-T

Position:

• chr11-6108607-C-T

Variant summary

Our verdict is Benign. Variant got -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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR56B4	NM_001005181.2	c.829C>T	p.Pro277Ser	missense_variant	1/1	ENST00000316529.3	NP_001005181.1
LOC124902622	XR_007062565.1	n.194+1657G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR56B4	ENST00000316529.3	c.829C>T	p.Pro277Ser	missense_variant	1/1		NM_001005181.2	ENSP00000321196	P1
	ENST00000529961.1	n.372-28G>A		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.523 AC: 131395 AN: 251468 Hom.: 37770 AF XY: 0.522 AC XY: 70939 AN XY: 135902

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 SAS exome AF: 0.605

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

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.689

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.856

Gnomad4 SAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.495

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.485

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

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.434

Alfa AF: 0.456 Hom.: 40068

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 v4.3

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
MutationTaster	Benign	1.0	P
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

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

Publications

LitVar

Other links and lift over

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