Variant 19-15807673-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013940.4(OR10H1):c.365G>A(p.Arg122His) variant causes a missense change. The variant allele was found at a frequency of 0.00132 in 1,613,986 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 13 hom. )

Consequence

OR10H1
NM_013940.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.55

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=0.005909294).

BP6

Variant 19-15807673-C-T is Benign according to our data. Variant chr19-15807673-C-T is described in ClinVar as [Benign]. Clinvar id is 782325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00696 (1059/152258) while in subpopulation AFR AF= 0.0239 (995/41546). AF 95% confidence interval is 0.0227. There are 6 homozygotes in gnomad4. There are 499 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10H1	NM_013940.4 link	c.365G>A	p.Arg122His	missense_variant	4/4	ENST00000641419.1	NP_039228.1	Q9Y4A9A0A126GVU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10H1	ENST00000641419.1 link	c.365G>A	p.Arg122His	missense_variant	4/4		NM_013940.4	ENSP00000493436.1		Q9Y4A9
OR10H1	ENST00000334920.3 link	c.365G>A	p.Arg122His	missense_variant	1/1	6		ENSP00000335596.2		Q9Y4A9

Frequencies

GnomAD3 genomes

AF:

0.00695

AC:

1057

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00189

AC:

474

AN:

250710

Hom.:

AF XY:

0.00142

AC XY:

192

AN XY:

135532

show subpopulations

Gnomad AFR exome

AF:

0.0252

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.000737

AC:

1078

AN:

1461728

Hom.:

Cov.:

AF XY:

0.000634

AC XY:

461

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0248

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000854

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00696

AC:

1059

AN:

152258

Hom.:

Cov.:

AF XY:

0.00670

AC XY:

499

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0239

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00318

Hom.:

Bravo

AF:

0.00812

ESP6500AA

AF:

0.0218

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00248

AC:

301

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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	Jun 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

.;T

MetaRNN

Benign

0.0059

T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-4.4

.;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.018

.;D

Sift4G

Uncertain

0.025

.;D

Polyphen

0.36

B;B

Vest4

0.63

MVP

0.78

MPC

0.75

ClinPred

0.052

GERP RS

4.7

Varity_R

0.32

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