15-101818248-G-A

Position:

• chr15-101818248-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001001674.2(OR4F15):​c.62G>A​(p.Arg21Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,613,838 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (25 hom.)
• Consequence: OR4F15 NM_001001674.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.476

Genes affected

OR4F15 (HGNC:15078): (olfactory receptor family 4 subfamily F member 15) 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004750639).
• BP6: Variant 15-101818248-G-A is Benign according to our data. Variant chr15-101818248-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00399 (5837/1461662) while in subpopulation MID AF= 0.0299 (172/5760). AF 95% confidence interval is 0.0262. There are 25 homozygotes in gnomad4_exome. There are 2944 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4F15	NM_001001674.2	c.62G>A	p.Arg21Gln	missense_variant	2/2	ENST00000332238.5	NP_001001674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4F15	ENST00000332238.5	c.62G>A	p.Arg21Gln	missense_variant	2/2	6	NM_001001674.2	ENSP00000333184.4

Frequencies

GnomAD3 genomes AF: 0.00359 AC: 546 AN: 152058 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00500

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00344 AC: 864 AN: 251020 Hom.: 3 AF XY: 0.00371 AC XY: 503 AN XY: 135650

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.00845

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00490

Gnomad OTH exome AF: 0.00801

GnomAD4 exome AF: 0.00399 AC: 5837 AN: 1461662 Hom.: 25 Cov.: 31 AF XY: 0.00405 AC XY: 2944 AN XY: 727126

Gnomad4 AFR exome AF: 0.00182

Gnomad4 AMR exome AF: 0.00369

Gnomad4 ASJ exome AF: 0.00892

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00162

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.00427

Gnomad4 OTH exome AF: 0.00523

GnomAD4 genome AF: 0.00358 AC: 545 AN: 152176 Hom.: 4 Cov.: 32 AF XY: 0.00331 AC XY: 246 AN XY: 74402

Gnomad4 AFR AF: 0.000867

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00500

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00514 Hom.: 10

Bravo AF: 0.00430

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00535 AC: 46

ExAC AF: 0.00335 AC: 407

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00616

EpiControl AF: 0.00646

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

OR4F15: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.00096	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.020	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.13
Sift	Benign	0.14	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.17
MVP		0.31
MPC		0.011
ClinPred		0.0051	T
GERP RS		4.4
Varity_R		0.045
gMVP		0.032

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: rs142759394; hg19: chr15-102358451;