8-166146-C-G

Variant names:

• chr8-166146-C-G
• NM_001005504.1:c.879G>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.879G>C​(p.Glu293Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 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: 1)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F21 NM_001005504.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.924
• 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=0.07121253).

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.879G>C	p.Glu293Asp	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.879G>C	p.Glu293Asp	missense	Exon 1 of 1	ENSP00000318878.3	O95013
	ENSG00000292979	ENST00000805562.1		n.115+65983G>C		intron	N/A
	ENSG00000292979	ENST00000805563.1		n.136+66830G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 12664 Hom.: 0 Cov.: 1

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: 0.0000129 AC: 4 AN: 310058 Hom.: 0 Cov.: 4 AF XY: 0.00000593 AC XY: 1 AN XY: 168592

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

African (AFR) AF: 0.00 AC: 0 AN: 15418

American (AMR) AF: 0.00 AC: 0 AN: 20312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8918

East Asian (EAS) AF: 0.00 AC: 0 AN: 14502

South Asian (SAS) AF: 0.00 AC: 0 AN: 35022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1168

European-Non Finnish (NFE) AF: 0.0000221 AC: 4 AN: 181216

Other (OTH) AF: 0.00 AC: 0 AN: 15730

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000222786), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 12664 Hom.: 0 Cov.: 1 AF XY: 0.00 AC XY: 0 AN XY: 5962

African (AFR) AF: 0.00 AC: 0 AN: 6690

American (AMR) AF: 0.00 AC: 0 AN: 424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 192

East Asian (EAS) AF: 0.00 AC: 0 AN: 52

South Asian (SAS) AF: 0.00 AC: 0 AN: 76

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 16

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4514

Other (OTH) AF: 0.00 AC: 0 AN: 96

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	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.53
DANN	Benign	0.63
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.00048	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L
PhyloP100		-0.92
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.066
Sift	Benign	0.68	T
Sift4G	Benign	0.43	T
Polyphen		0.011	B
Vest4		0.12
MutPred		0.67		Gain of MoRF binding (P = 0.0888)
MVP		0.048
ClinPred		0.029	T
GERP RS		-2.7
Varity_R		0.037
gMVP		0.13
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

hg19: chr8-116146;