19-15807673-C-T

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

11
7

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]

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
OR10H1NM_013940.4 linkc.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
OR10H1ENST00000641419.1 linkc.365G>A p.Arg122His missense_variant 4/4 NM_013940.4 ENSP00000493436.1 Q9Y4A9
OR10H1ENST00000334920.3 linkc.365G>A p.Arg122His missense_variant 1/16 ENSP00000335596.2 Q9Y4A9

Frequencies

GnomAD3 genomes
AF:
0.00695
AC:
1057
AN:
152140
Hom.:
6
Cov.:
32
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.:
7
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.:
13
Cov.:
60
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.:
6
Cov.:
32
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.:
0
Bravo
AF:
0.00812
ESP6500AA
AF:
0.0218
AC:
96
ESP6500EA
AF:
0.000233
AC:
2
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 21, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
T;T
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.82
.;T
MetaRNN
Benign
0.0059
T;T
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Uncertain
2.5
M;M
PrimateAI
Benign
0.23
T
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
T
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.

Other links and lift over

dbSNP: rs61746482; hg19: chr19-15918483; API