chr19-15807539-C-T

Position:

• chr19-15807539-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013940.4(OR10H1):​c.499G>A​(p.Ala167Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,614,198 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A167D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.017 (72 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (66 hom.)
• Consequence: OR10H1 NM_013940.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026288033).
• BP6: Variant 19-15807539-C-T is Benign according to our data. Variant chr19-15807539-C-T is described in ClinVar as [Benign]. Clinvar id is 716474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10H1	NM_013940.4	c.499G>A	p.Ala167Thr	missense_variant	4/4	ENST00000641419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10H1	ENST00000641419.1	c.499G>A	p.Ala167Thr	missense_variant	4/4		NM_013940.4	P1
OR10H1	ENST00000334920.3	c.499G>A	p.Ala167Thr	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2519 AN: 152202 Hom.: 72 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00466 AC: 1171 AN: 251482 Hom.: 24 AF XY: 0.00349 AC XY: 475 AN XY: 135918

Gnomad AFR exome AF: 0.0591

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00647

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00186 AC: 2713 AN: 1461878 Hom.: 66 Cov.: 31 AF XY: 0.00160 AC XY: 1164 AN XY: 727238

Gnomad4 AFR exome AF: 0.0593

Gnomad4 AMR exome AF: 0.00253

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00831

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000629

Gnomad4 OTH exome AF: 0.00334

GnomAD4 genome AF: 0.0166 AC: 2523 AN: 152320 Hom.: 72 Cov.: 32 AF XY: 0.0156 AC XY: 1160 AN XY: 74472

Gnomad4 AFR AF: 0.0565

Gnomad4 AMR AF: 0.00719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00502

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00309 Hom.: 7

Bravo AF: 0.0184

ESP6500AA AF: 0.0581 AC: 256

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00572 AC: 694

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.65
DEOGEN2	Benign	0.00020	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.041	.;T
MetaRNN	Benign	0.0026	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.60	.;N
REVEL	Benign	0.018
Sift	Benign	0.42	.;T
Sift4G	Benign	0.24	.;T
Polyphen		0.0	B;B
Vest4		0.054
MVP		0.14
MPC		0.50
ClinPred		0.0029	T
GERP RS		-5.5
Varity_R		0.044

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

Other links and lift over

dbSNP: rs61745313; hg19: chr19-15918349;