15-101922266-G-C

Position:

• chr15-101922266-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000650172.1(OR4F4):​c.848C>G​(p.Ala283Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000072 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F4 ENST00000650172.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13

Genes affected

OR4F4 (HGNC:8301): (olfactory receptor family 4 subfamily F member 4) 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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25414664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4F4	ENST00000650172.1	c.848C>G	p.Ala283Gly	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 139654 Hom.: 0 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000426 AC: 6 AN: 1406850 Hom.: 0 Cov.: 29 AF XY: 0.00000854 AC XY: 6 AN XY: 702594

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000374

Gnomad4 OTH exome AF: 0.0000343

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000716 AC: 1 AN: 139654 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 67974

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000151

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.794C>G (p.A265G) alteration is located in exon 1 (coding exon 1) of the OR4F4 gene. This alteration results from a C to G substitution at nucleotide position 794, causing the alanine (A) at amino acid position 265 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;.
Eigen	Benign	-0.089
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.00080	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.0	M;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.9	D;.
REVEL	Benign	0.059
Sift	Uncertain	0.022	D;.
Sift4G	Uncertain	0.011	D;.
Polyphen		1.0	D;.
Vest4		0.34
MutPred		0.62		Loss of stability (P = 0.0342);.;
MVP		0.52
ClinPred		0.87	D
GERP RS		1.6
Varity_R		0.20
gMVP		0.063

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: rs1212446141; hg19: chr15-102462469;