8-166370-C-T

Variant names:

• chr8-166370-C-T
• rs1475792281
• NM_001005504.1:c.655G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001005504.1(OR4F21):​c.655G>A​(p.Val219Ile) 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (1 hom., cov: 4)
  • Exomes 𝑓: 0.047 (341 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F21 NM_001005504.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034701735).
• BP6: Variant 8-166370-C-T is Benign according to our data. Variant chr8-166370-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2343404.Status of the report is criteria_provided_single_submitter, 1 stars.

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.655G>A	p.Val219Ile	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.655G>A	p.Val219Ile	missense	Exon 1 of 1	ENSP00000318878.3	O95013
	ENSG00000292979	ENST00000805562.1		n.115+65759G>A		intron	N/A
	ENSG00000292979	ENST00000805563.1		n.136+66606G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 1128 AN: 15428 Hom.: 1 Cov.: 4

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0444

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.0293

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0351

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.0227

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0619

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0472 AC: 17422 AN: 369406 Hom.: 341 Cov.: 0 AF XY: 0.0457 AC XY: 8833 AN XY: 193244

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

African (AFR) AF: 0.123 AC: 1096 AN: 8940

American (AMR) AF: 0.0771 AC: 1172 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.0336 AC: 399 AN: 11862

East Asian (EAS) AF: 0.164 AC: 3681 AN: 22506

South Asian (SAS) AF: 0.0353 AC: 1286 AN: 36440

European-Finnish (FIN) AF: 0.0501 AC: 1234 AN: 24624

Middle Eastern (MID) AF: 0.0249 AC: 42 AN: 1690

European-Non Finnish (NFE) AF: 0.0332 AC: 7530 AN: 226528

Other (OTH) AF: 0.0454 AC: 982 AN: 21616

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0734 AC: 1135 AN: 15462 Hom.: 1 Cov.: 4 AF XY: 0.0743 AC XY: 525 AN XY: 7062

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

African (AFR) AF: 0.116 AC: 682 AN: 5904

American (AMR) AF: 0.0907 AC: 94 AN: 1036

Ashkenazi Jewish (ASJ) AF: 0.0293 AC: 12 AN: 410

East Asian (EAS) AF: 0.136 AC: 27 AN: 198

South Asian (SAS) AF: 0.0348 AC: 8 AN: 230

European-Finnish (FIN) AF: 0.0811 AC: 107 AN: 1320

Middle Eastern (MID) AF: 0.0256 AC: 2 AN: 78

European-Non Finnish (NFE) AF: 0.0312 AC: 187 AN: 5988

Other (OTH) AF: 0.0577 AC: 12 AN: 208

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.069
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.75
DANN	Benign	0.55
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.00095	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.61	N
PhyloP100		-1.2
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.013
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.060
MVP		0.030
ClinPred		0.024	T
GERP RS		-1.1
Varity_R		0.021
gMVP		0.054
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: rs1475792281; hg19: chr8-116370; COSMIC: COSV57994342;