19-14827332-G-A

Position:

chr19-14827332-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017506.2(OR7A5):c.910C>T(p.His304Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000275 in 1,584,366 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

OR7A5
NM_017506.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.94

Variant links:

Genes affected

OR7A5 (HGNC:8368): (olfactory receptor family 7 subfamily A member 5) 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]

OR7A5 links:

OR7C1 (HGNC:8373): (olfactory receptor family 7 subfamily C 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]

OR7C1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020311117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR7A5	NM_017506.2 link	c.910C>T	p.His304Tyr	missense_variant	2/2	ENST00000322301.5	NP_059976.1	Q15622A0A126GW60
OR7C1	NM_001370485.4 link	c.-623+7742C>T		intron_variant		ENST00000641666.2	NP_001357414.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR7A5	ENST00000322301.5 link	c.910C>T	p.His304Tyr	missense_variant	2/2	6	NM_017506.2	ENSP00000316955.3		Q15622
OR7C1	ENST00000641666.2 link	c.-623+7742C>T		intron_variant			NM_001370485.4	ENSP00000493429.1		O76099

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000269

AC:

AN:

223148

Hom.:

AF XY:

0.000266

AC XY:

AN XY:

120326

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000353

Gnomad ASJ exome

AF:

0.00105

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000501

Gnomad NFE exome

AF:

0.000462

Gnomad OTH exome

AF:

0.000375

GnomAD4 exome

AF:

0.000270

AC:

387

AN:

1432206

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

206

AN XY:

710974

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000262

Gnomad4 ASJ exome

AF:

0.00155

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000172

Gnomad4 NFE exome

AF:

0.000294

Gnomad4 OTH exome

AF:

0.000271

GnomAD4 genome

AF:

0.000322

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000528

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000313

AC:

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

Jun 11, 2021

The c.910C>T (p.H304Y) alteration is located in exon 1 (coding exon 1) of the OR7A5 gene. This alteration results from a C to T substitution at nucleotide position 910, causing the histidine (H) at amino acid position 304 to be replaced by a tyrosine (Y). 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

0.071

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.033

DANN

Benign

0.32

DEOGEN2

Benign

0.0038

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.17

.;T

M_CAP

Benign

0.00082

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.60

N;.

REVEL

Benign

0.025

Sift

Benign

0.46

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0040

B;B

Vest4

0.11

MVP

0.26

MPC

0.059

ClinPred

0.027

GERP RS

-5.0

Varity_R

0.022

gMVP

0.031

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