Variant 7-144004447-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001005281.3(OR6B1):c.451A>G(p.Ile151Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,614,104 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00084 ( 2 hom. )

Consequence

OR6B1
NM_001005281.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.211

Variant links:

Genes affected

OR6B1 (HGNC:8354): (olfactory receptor family 6 subfamily B 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]

OR6B1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027748644).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR6B1	NM_001005281.3 link	c.451A>G	p.Ile151Val	missense_variant	2/2	ENST00000641698.1	NP_001005281.1	O95007

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6B1	ENST00000641698.1 link	c.451A>G	p.Ile151Val	missense_variant	2/2		NM_001005281.3	ENSP00000492907.1		O95007
OR6B1	ENST00000408922.3 link	c.451A>G	p.Ile151Val	missense_variant	1/1	6		ENSP00000386151.2		O95007

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000486

AC:

121

AN:

249140

Hom.:

AF XY:

0.000555

AC XY:

AN XY:

135122

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.000807

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000840

AC:

1228

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000837

AC XY:

609

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000626

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.000990

Gnomad4 OTH exome

AF:

0.000811

GnomAD4 genome

AF:

0.000401

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000721

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000712

Hom.:

Bravo

AF:

0.000306

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000235

AC:

ESP6500EA

AF:

0.000586

AC:

ExAC

AF:

0.000454

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000889

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.451A>G (p.I151V) alteration is located in exon 1 (coding exon 1) of the OR6B1 gene. This alteration results from a A to G substitution at nucleotide position 451, causing the isoleucine (I) at amino acid position 151 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.8

DANN

Benign

0.79

DEOGEN2

Benign

0.0013

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.059

M_CAP

Benign

0.0052

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.27

N;N

PrimateAI

Benign

0.17

PROVEAN

Benign

0.41

.;N

REVEL

Benign

0.018

Sift

Benign

0.16

.;T

Sift4G

Benign

0.31

.;T

Polyphen

0.0

B;B

Vest4

0.096

MVP

0.33

MPC

0.080

ClinPred

0.0044

GERP RS

2.9

Varity_R

0.046

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over