8-166096-T-C

Variant names:

• chr8-166096-T-C
• rs199977572
• NM_001005504.1:c.929A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005504.1(OR4F21):​c.929A>G​(p.Lys310Arg) 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 0.0043 (9 hom., cov: 1)
  • Exomes 𝑓: 0.0079 (343 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F21 NM_001005504.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0730
• Publications: 2 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.060744673).

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.929A>G	p.Lys310Arg	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.929A>G	p.Lys310Arg	missense	Exon 1 of 1	ENSP00000318878.3	O95013
	ENSG00000292979	ENST00000805562.1		n.115+66033A>G		intron	N/A
	ENSG00000292979	ENST00000805563.1		n.136+66880A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00428 AC: 65 AN: 15192 Hom.: 9 Cov.: 1

Gnomad AFR AF: 0.00277

Gnomad AMI AF: 0.0345

Gnomad AMR AF: 0.00951

Gnomad ASJ AF: 0.00431

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00631

Gnomad OTH AF: 0.00714

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00790 AC: 2275 AN: 287860 Hom.: 343 Cov.: 4 AF XY: 0.00739 AC XY: 1129 AN XY: 152760

African (AFR) AF: 0.00202 AC: 40 AN: 19762

American (AMR) AF: 0.00320 AC: 54 AN: 16870

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 7 AN: 6554

East Asian (EAS) AF: 0.000369 AC: 4 AN: 10846

South Asian (SAS) AF: 0.00137 AC: 34 AN: 24800

European-Finnish (FIN) AF: 0.000446 AC: 6 AN: 13440

Middle Eastern (MID) AF: 0.000978 AC: 1 AN: 1022

European-Non Finnish (NFE) AF: 0.0113 AC: 2050 AN: 180864

Other (OTH) AF: 0.00577 AC: 79 AN: 13702

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00427 AC: 65 AN: 15226 Hom.: 9 Cov.: 1 AF XY: 0.00365 AC XY: 26 AN XY: 7122

African (AFR) AF: 0.00276 AC: 21 AN: 7620

American (AMR) AF: 0.00951 AC: 5 AN: 526

Ashkenazi Jewish (ASJ) AF: 0.00431 AC: 1 AN: 232

East Asian (EAS) AF: 0.00 AC: 0 AN: 50

South Asian (SAS) AF: 0.00 AC: 0 AN: 112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 24

European-Non Finnish (NFE) AF: 0.00631 AC: 35 AN: 5544

Other (OTH) AF: 0.00704 AC: 1 AN: 142

Alfa AF: 0.00497 Hom.: 2

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	0.063
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.6
DANN	Benign	0.95
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.00042	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.073
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.020
Sift	Benign	0.14	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.38		Loss of methylation at K310 (P = 0.0046)
MVP		0.040
ClinPred		0.043	T
GERP RS		-1.4
Varity_R		0.056
gMVP		0.037
Mutation Taster		=99/1	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: rs199977572; hg19: chr8-116096; COSMIC: COSV100307503;