NM_001005504.1:c.691G>C

Variant names:

• chr8-166334-C-G
• rs1465927356
• NM_001005504.1:c.691G>C

Variant summary

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

The NM_001005504.1(OR4F21):​c.691G>C​(p.Gly231Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 4)
  • Exomes 𝑓: 0.000028 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F21 NM_001005504.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.213
• 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=0.08693203).

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.691G>C	p.Gly231Arg	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.691G>C	p.Gly231Arg	missense	Exon 1 of 1	ENSP00000318878.3	O95013
	ENSG00000292979	ENST00000805562.1		n.115+65795G>C		intron	N/A
	ENSG00000292979	ENST00000805563.1		n.136+66642G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 15526 Hom.: 0 Cov.: 4

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000281 AC: 11 AN: 391504 Hom.: 1 Cov.: 0 AF XY: 0.0000391 AC XY: 8 AN XY: 204402

African (AFR) AF: 0.000169 AC: 2 AN: 11802

American (AMR) AF: 0.0000592 AC: 1 AN: 16898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12766

East Asian (EAS) AF: 0.00 AC: 0 AN: 24262

South Asian (SAS) AF: 0.0000535 AC: 2 AN: 37406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 237200

Other (OTH) AF: 0.000261 AC: 6 AN: 22970

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 15566 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 7154

African (AFR) AF: 0.00 AC: 0 AN: 7914

American (AMR) AF: 0.00 AC: 0 AN: 820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 298

East Asian (EAS) AF: 0.00 AC: 0 AN: 170

South Asian (SAS) AF: 0.00 AC: 0 AN: 178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 60

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4960

Other (OTH) AF: 0.00 AC: 0 AN: 178

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	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.00084	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.61	N
PhyloP100		-0.21
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.034
Sift	Uncertain	0.020	D
Sift4G	Benign	0.16	T
Polyphen		0.031	B
Vest4		0.11
MutPred		0.45		Gain of MoRF binding (P = 0.0087)
MVP		0.35
ClinPred		0.26	T
GERP RS		1.0
Varity_R		0.43
gMVP		0.086
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

dbSNP: rs1465927356; hg19: chr8-116334;