chr8-166463-C-T

Variant names:

• chr8-166463-C-T
• NM_001005504.1:c.562G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001005504.1(OR4F21):​c.562G>A​(p.Ala188Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 6)
  • Exomes 𝑓: 0.0000023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F21 NM_001005504.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0710
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28249687).

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.562G>A	p.Ala188Thr	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.562G>A	p.Ala188Thr	missense	Exon 1 of 1	ENSP00000318878.3	O95013
	ENSG00000292979	ENST00000805562.1		n.115+65666G>A		intron	N/A
	ENSG00000292979	ENST00000805563.1		n.136+66513G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000227 AC: 1 AN: 440268 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 233046

African (AFR) AF: 0.00 AC: 0 AN: 12798

American (AMR) AF: 0.0000443 AC: 1 AN: 22568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14264

East Asian (EAS) AF: 0.00 AC: 0 AN: 27432

South Asian (SAS) AF: 0.00 AC: 0 AN: 42524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1912

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 264054

Other (OTH) AF: 0.00 AC: 0 AN: 25262

GnomAD4 genome Cov.: 6

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	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.056
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.078	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.00062	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.071
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.051
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.78	P
Vest4		0.47
MutPred		0.57		Loss of stability (P = 0.0652)
MVP		0.085
ClinPred		0.95	D
GERP RS		2.0
Varity_R		0.24
gMVP		0.089
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr8-116463;