8-166217-A-T

Position:

• chr8-166217-A-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001005504.1(OR4F21):​c.808T>A​(p.Phe270Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 2)
• Consequence: OR4F21 NM_001005504.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.823

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26520324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4F21	NM_001005504.1	c.808T>A	p.Phe270Ile	missense_variant	1/1	ENST00000320901.4	NP_001005504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4F21	ENST00000320901.4	c.808T>A	p.Phe270Ile	missense_variant	1/1	6	NM_001005504.1	ENSP00000318878.3

Frequencies

GnomAD3 genomes Cov.: 2

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.808T>A (p.F270I) alteration is located in exon 1 (coding exon 1) of the OR4F21 gene. This alteration results from a T to A substitution at nucleotide position 808, causing the phenylalanine (F) at amino acid position 270 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.00078	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.84	L
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.068
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.25
MutPred		0.24		Loss of ubiquitination at K269 (P = 0.1151);
MVP		0.061
ClinPred		0.95	D
GERP RS		2.0
Varity_R		0.58
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-116217;