Variant X-131544809-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001004486.1(OR13H1):c.736G>A(p.Val246Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,208,604 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000033 ( 0 hom. 9 hem. )

Consequence

OR13H1
NM_001004486.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.768

Variant links:

Genes affected

OR13H1 (HGNC:14755): (olfactory receptor family 13 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]

OR13H1 links:

IGSF1 (HGNC:5948): (immunoglobulin superfamily member 1) This gene encodes a member of the immunoglobulin-like domain-containing superfamily. Proteins in this superfamily contain varying numbers of immunoglobulin-like domains and are thought to participate in the regulation of interactions between cells. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

IGSF1 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=0.060419023).

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR13H1	NM_001004486.1 linkuse as main transcript	c.736G>A	p.Val246Met	missense_variant	1/1	ENST00000338616.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR13H1	ENST00000338616.6 linkuse as main transcript	c.736G>A	p.Val246Met	missense_variant	1/1		NM_001004486.1	P1
IGSF1	ENST00000370904.6 linkuse as main transcript	c.-913+33859C>T		intron_variant		2			Q8N6C5-2

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111445

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33631

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000282

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

182045

Hom.:

AF XY:

0.0000750

AC XY:

AN XY:

66701

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00108

Gnomad SAS exome

AF:

0.000106

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1097159

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

362543

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000853

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000265

Gnomad4 SAS exome

AF:

0.000167

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000190

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000897

AC:

AN:

111445

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33631

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.000107

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.78

M_CAP

Benign

0.0027

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.059

MutPred

0.44

Gain of MoRF binding (P = 0.3528);

MVP

0.44

MPC

0.17

ClinPred

0.32

GERP RS

3.1

Varity_R

0.42

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over