19-15794466-G-A

Position:

• chr19-15794466-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001004466.2(OR10H5):​c.418G>A​(p.Gly140Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,614,230 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (31 hom.)
• Consequence: OR10H5 NM_001004466.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.168

Genes affected

OR10H5 (HGNC:15389): (olfactory receptor family 10 subfamily H 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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007007122).
• BP6: Variant 19-15794466-G-A is Benign according to our data. Variant chr19-15794466-G-A is described in ClinVar as [Benign]. Clinvar id is 710142.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 = 0.0118 (1793/152348) while in subpopulation AFR AF= 0.041 (1703/41568). AF 95% confidence interval is 0.0393. There are 30 homozygotes in gnomad4. There are 844 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10H5	NM_001004466.2	c.418G>A	p.Gly140Ser	missense_variant	2/2	ENST00000642092.2	NP_001004466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10H5	ENST00000642092.2	c.418G>A	p.Gly140Ser	missense_variant	2/2		NM_001004466.2	ENSP00000493242.1
OR10H5	ENST00000308940.8	c.418G>A	p.Gly140Ser	missense_variant	1/1	6		ENSP00000310704.8

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1789 AN: 152230 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00298 AC: 750 AN: 251404 Hom.: 12 AF XY: 0.00222 AC XY: 301 AN XY: 135878

Gnomad AFR exome AF: 0.0416

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000703

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00118 AC: 1722 AN: 1461882 Hom.: 31 Cov.: 89 AF XY: 0.000978 AC XY: 711 AN XY: 727242

Gnomad4 AFR exome AF: 0.0417

Gnomad4 AMR exome AF: 0.00174

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000629

Gnomad4 OTH exome AF: 0.00255

GnomAD4 genome AF: 0.0118 AC: 1793 AN: 152348 Hom.: 30 Cov.: 32 AF XY: 0.0113 AC XY: 844 AN XY: 74500

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00336 Hom.: 3

Bravo AF: 0.0135

ESP6500AA AF: 0.0409 AC: 180

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00380 AC: 461

Asia WGS AF: 0.00144 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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	Oct 09, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.00012	T;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.23	.;T
MetaRNN	Benign	0.0070	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.2	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.88	.;N
REVEL	Benign	0.068
Sift	Benign	0.22	.;T
Sift4G	Benign	0.28	.;T
Polyphen		0.057	B;B
Vest4		0.047
MVP		0.26
MPC		0.32
ClinPred		0.0081	T
GERP RS		3.3
Varity_R		0.065
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs61754880; hg19: chr19-15905276; COSMIC: COSV99079700;