chr8-166508-C-T

Variant names:

• chr8-166508-C-T
• rs903223734
• NM_001005504.1:c.517G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005504.1(OR4F21):​c.517G>A​(p.Val173Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000068 (0 hom., cov: 6)
  • Exomes 𝑓: 0.000055 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F21 NM_001005504.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.18
• Publications: 0 publications found

Genes affected

OR4F21 (HGNC:19583): (olfactory receptor family 4 subfamily F member 21) 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]

ENSG00000292979 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10660115).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005504.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4F21	NM_001005504.1	MANE Select	c.517G>A	p.Val173Met	missense	Exon 1 of 1	NP_001005504.1	O95013

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4F21	ENST00000320901.4	TSL:6 MANE Select	c.517G>A	p.Val173Met	missense	Exon 1 of 1	ENSP00000318878.3	O95013
	ENSG00000292979	ENST00000805562.1		n.115+65621G>A		intron	N/A
	ENSG00000292979	ENST00000805563.1		n.136+66468G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000681 AC: 3 AN: 44060 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.0000754

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: 0.0000476

Gnomad OTH AF: 0.00231

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000545 AC: 38 AN: 696850 Hom.: 4 Cov.: 9 AF XY: 0.0000493 AC XY: 18 AN XY: 364914

African (AFR) AF: 0.0000536 AC: 1 AN: 18646

American (AMR) AF: 0.00 AC: 0 AN: 37530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20084

East Asian (EAS) AF: 0.00 AC: 0 AN: 29898

South Asian (SAS) AF: 0.00 AC: 0 AN: 57590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2608

European-Non Finnish (NFE) AF: 0.0000802 AC: 37 AN: 461242

Other (OTH) AF: 0.00 AC: 0 AN: 34342

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000681 AC: 3 AN: 44060 Hom.: 0 Cov.: 6 AF XY: 0.0000487 AC XY: 1 AN XY: 20522

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000754 AC: 1 AN: 13262

American (AMR) AF: 0.00 AC: 0 AN: 3448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1388

East Asian (EAS) AF: 0.00 AC: 0 AN: 636

South Asian (SAS) AF: 0.00 AC: 0 AN: 508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 106

European-Non Finnish (NFE) AF: 0.0000476 AC: 1 AN: 21010

Other (OTH) AF: 0.00231 AC: 1 AN: 432

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0232839), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.00048	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.078
Sift	Benign	0.16	T
Sift4G	Benign	0.069	T
Polyphen		0.41	B
Vest4		0.14
MutPred		0.43		Loss of catalytic residue at V173 (P = 0.1667)
MVP		0.10
ClinPred		0.30	T
GERP RS		1.0
Varity_R		0.053
gMVP		0.064
Mutation Taster		=100/0	polymorphism

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: rs903223734; hg19: chr8-116508;