14-20117883-G-C

Variant names:

• chr14-20117883-G-C
• rs8005245
• NM_001004715.5:c.384G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004715.5(OR4K17):​c.384G>C​(p.Lys128Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,613,370 control chromosomes in the GnomAD database, including 140,052 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (12323 hom., cov: 31)
  • Exomes 𝑓: 0.42 (127729 hom.)
• Consequence: OR4K17 NM_001004715.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.98
• Publications: 25 publications found

Genes affected

OR4K17 (HGNC:15355): (olfactory receptor family 4 subfamily K member 17) 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.5277404E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4K17	NM_001004715.5	c.384G>C	p.Lys128Asn	missense_variant	Exon 2 of 2	ENST00000641386.2	NP_001004715.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4K17	ENST00000641386.2	c.384G>C	p.Lys128Asn	missense_variant	Exon 2 of 2		NM_001004715.5	ENSP00000493449.2
OR4K17	ENST00000641633.2	c.384G>C	p.Lys128Asn	missense_variant	Exon 3 of 3			ENSP00000493115.2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60668 AN: 151592 Hom.: 12312 Cov.: 31

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.420

GnomAD2 exomes AF: 0.428 AC: 107273 AN: 250890 AF XY: 0.431

Gnomad AFR exome AF: 0.352

Gnomad AMR exome AF: 0.421

Gnomad ASJ exome AF: 0.404

Gnomad EAS exome AF: 0.573

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.413

Gnomad OTH exome AF: 0.429

GnomAD4 exome AF: 0.417 AC: 609265 AN: 1461656 Hom.: 127729 Cov.: 46 AF XY: 0.419 AC XY: 304897 AN XY: 727124

African (AFR) AF: 0.352 AC: 11785 AN: 33476

American (AMR) AF: 0.420 AC: 18772 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 10630 AN: 26132

East Asian (EAS) AF: 0.528 AC: 20942 AN: 39694

South Asian (SAS) AF: 0.468 AC: 40395 AN: 86256

European-Finnish (FIN) AF: 0.400 AC: 21375 AN: 53414

Middle Eastern (MID) AF: 0.481 AC: 2775 AN: 5768

European-Non Finnish (NFE) AF: 0.411 AC: 457026 AN: 1111822

Other (OTH) AF: 0.423 AC: 25565 AN: 60380

GnomAD4 genome AF: 0.400 AC: 60710 AN: 151714 Hom.: 12323 Cov.: 31 AF XY: 0.398 AC XY: 29525 AN XY: 74120

African (AFR) AF: 0.350 AC: 14447 AN: 41318

American (AMR) AF: 0.425 AC: 6480 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3466

East Asian (EAS) AF: 0.558 AC: 2879 AN: 5164

South Asian (SAS) AF: 0.472 AC: 2264 AN: 4792

European-Finnish (FIN) AF: 0.390 AC: 4091 AN: 10486

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27789 AN: 67940

Other (OTH) AF: 0.419 AC: 885 AN: 2112

Alfa AF: 0.406 Hom.: 4094

Bravo AF: 0.404

TwinsUK AF: 0.410 AC: 1520

ALSPAC AF: 0.427 AC: 1647

ESP6500AA AF: 0.362 AC: 1596

ESP6500EA AF: 0.417 AC: 3585

ExAC AF: 0.426 AC: 51682

Asia WGS AF: 0.451 AC: 1572 AN: 3478

EpiCase AF: 0.405

EpiControl AF: 0.408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Uncertain	1.0
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.19	.;.;T
MetaRNN	Benign	0.000055	T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		-4.0
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-4.4	.;.;D
REVEL	Benign	0.047
Sift	Pathogenic	0.0	.;.;D
Sift4G	Benign	0.064	.;.;T
Vest4		0.051
MPC		0.0013
ClinPred		0.048	T
GERP RS		1.9
gMVP		0.070
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8005245; hg19: chr14-20586042; COSMIC: COSV59647561;