rs79869455

chr1-158420751-A-Cchr1-158420751-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001004476.2(OR10K2):c.116T>G(p.Leu39Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00157 in 1,613,768 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0081 (18 hom., cov: 31)
  • Exomes 𝑓: 0.00089 (23 hom.)
• Consequence: OR10K2 NM_001004476.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.02

Genes affected

OR10K2 (HGNC:14826): (olfactory receptor family 10 subfamily K member 2) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049262643).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00812 (1236/152176) while in subpopulation AFR AF= 0.0286 (1186/41536). AF 95% confidence interval is 0.0272. There are 18 homozygotes in gnomad4. There are 548 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10K2	NM_001004476.2	c.116T>G	p.Leu39Arg	missense_variant	2/2	ENST00000641042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10K2	ENST00000641042.1	c.116T>G	p.Leu39Arg	missense_variant	2/2		NM_001004476.2	P1

Frequencies

GnomAD3 genomes AF: 0.00812 AC: 1234 AN: 152058 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

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: 0.0000588

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00212 AC: 532 AN: 251120 Hom.: 9 AF XY: 0.00151 AC XY: 205 AN XY: 135714

Gnomad AFR exome AF: 0.0292

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000893 AC: 1305 AN: 1461592 Hom.: 23 Cov.: 33 AF XY: 0.000761 AC XY: 553 AN XY: 727098

Gnomad4 AFR exome AF: 0.0322

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.00224

GnomAD4 genome AF: 0.00812 AC: 1236 AN: 152176 Hom.: 18 Cov.: 31 AF XY: 0.00737 AC XY: 548 AN XY: 74402

Gnomad4 AFR AF: 0.0286

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.000670 Hom.: 0

Bravo AF: 0.00916

ESP6500AA AF: 0.0259 AC: 114

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00238 AC: 289

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.38
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.63	D
MetaRNN	Benign	0.0049	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.9	H;H
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.29	T
Polyphen		1.0	D;D
Vest4		0.81
MVP		0.63
MPC		0.032
ClinPred		0.093	T
GERP RS		4.1
Varity_R		0.98
gMVP		0.25

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: rs79869455; hg19: chr1-158390541;