Variant chr19-15807367-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013940.4(OR10H1):c.671C>A(p.Ala224Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 151,432 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 74 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 32 hom. )

Failed GnomAD Quality Control

Consequence

OR10H1
NM_013940.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.107

Variant links:

Genes affected

OR10H1 (HGNC:8172): (olfactory receptor family 10 subfamily H 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]

OR10H1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005328417).

BP6

Variant 19-15807367-G-T is Benign according to our data. Variant chr19-15807367-G-T is described in ClinVar as [Benign]. Clinvar id is 716473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10H1	NM_013940.4 linkuse as main transcript	c.671C>A	p.Ala224Asp	missense_variant	4/4	ENST00000641419.1	NP_039228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10H1	ENST00000641419.1 linkuse as main transcript	c.671C>A	p.Ala224Asp	missense_variant	4/4		NM_013940.4	ENSP00000493436	P1
OR10H1	ENST00000334920.3 linkuse as main transcript	c.671C>A	p.Ala224Asp	missense_variant	1/1			ENSP00000335596	P1

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2558

AN:

151314

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0573

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00939

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00138

Gnomad SAS

AF:

0.000627

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0136

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00289

AC:

3962

AN:

1372004

Hom.:

Cov.:

AF XY:

0.00276

AC XY:

1884

AN XY:

683140

show subpopulations

Gnomad4 AFR exome

AF:

0.0598

Gnomad4 AMR exome

AF:

0.0126

Gnomad4 ASJ exome

AF:

0.00109

Gnomad4 EAS exome

AF:

0.00772

Gnomad4 SAS exome

AF:

0.000871

Gnomad4 FIN exome

AF:

0.000348

Gnomad4 NFE exome

AF:

0.000841

Gnomad4 OTH exome

AF:

0.00447

GnomAD4 genome

AF:

0.0169

AC:

2562

AN:

151432

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1188

AN XY:

73986

show subpopulations

Gnomad4 AFR

AF:

0.0572

Gnomad4 AMR

AF:

0.00938

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00138

Gnomad4 SAS

AF:

0.000628

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0135

Alfa

AF:

0.00863

Hom.:

Bravo

AF:

0.0184

ExAC

AF:

0.0244

AC:

2963

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.034

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.20

.;T

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.0

.;N

REVEL

Benign

0.24

Sift

Uncertain

0.0040

.;D

Sift4G

Uncertain

0.017

.;D

Polyphen

0.96

D;D

Vest4

0.076

MPC

1.5

ClinPred

0.047

GERP RS

2.8

Varity_R

0.52

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

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