8-166570-C-G

Variant names:

• chr8-166570-C-G
• rs1033118821
• NM_001005504.1:c.455G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001005504.1(OR4F21):​c.455G>C​(p.Gly152Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (1 hom., cov: 6)
  • Exomes 𝑓: 0.000051 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F21 NM_001005504.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.903
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

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.455G>C	p.Gly152Ala	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.455G>C	p.Gly152Ala	missense	Exon 1 of 1	ENSP00000318878.3	O95013
	ENSG00000292979	ENST00000805562.1		n.115+65559G>C		intron	N/A
	ENSG00000292979	ENST00000805563.1		n.136+66406G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000219 AC: 11 AN: 50182 Hom.: 1 Cov.: 6

Gnomad AFR AF: 0.000706

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 740 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000510 AC: 29 AN: 568390 Hom.: 7 Cov.: 7 AF XY: 0.0000295 AC XY: 9 AN XY: 304630

African (AFR) AF: 0.00164 AC: 28 AN: 17042

American (AMR) AF: 0.00 AC: 0 AN: 32448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17550

East Asian (EAS) AF: 0.00 AC: 0 AN: 29840

South Asian (SAS) AF: 0.00 AC: 0 AN: 52162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2250

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 352850

Other (OTH) AF: 0.0000332 AC: 1 AN: 30096

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000219 AC: 11 AN: 50182 Hom.: 1 Cov.: 6 AF XY: 0.000297 AC XY: 7 AN XY: 23564

African (AFR) AF: 0.000706 AC: 11 AN: 15574

American (AMR) AF: 0.00 AC: 0 AN: 3498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1632

East Asian (EAS) AF: 0.00 AC: 0 AN: 782

South Asian (SAS) AF: 0.00 AC: 0 AN: 602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 74

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 24466

Other (OTH) AF: 0.00 AC: 0 AN: 578

Alfa AF: 0.000337 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	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0016	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.90
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.71		Gain of catalytic residue at G152 (P = 0.1485)
MVP		0.22
ClinPred		0.94	D
GERP RS		2.0
PromoterAI		0.0090	Neutral
Varity_R		0.44
gMVP		0.12
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1033118821; hg19: chr8-116570;