chr11-55368200-C-T

Variant names:

• chr11-55368200-C-T
• rs745361366
• NM_001005275.2:c.227C>T

Variant summary

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

The NM_001005275.2(OR4A15):​c.227C>T​(p.Ala76Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000769 in 1,613,468 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000081 (0 hom.)
• Consequence: OR4A15 NM_001005275.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.464
• Publications: 1 publications found

Genes affected

OR4A15 (HGNC:15152): (olfactory receptor family 4 subfamily A member 15) 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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06153944).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005275.2. 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
	OR4A15	NM_001005275.2	MANE Select	c.227C>T	p.Ala76Val	missense	Exon 1 of 1	NP_001005275.2	A0A286YF59

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4A15	ENST00000641526.1	MANE Select	c.227C>T	p.Ala76Val	missense	Exon 1 of 1	ENSP00000493060.1	A0A286YF59

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000588

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000918 AC: 23 AN: 250672 AF XY: 0.0000591

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.0000807 AC: 118 AN: 1461356 Hom.: 0 Cov.: 33 AF XY: 0.0000784 AC XY: 57 AN XY: 726986

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000244 AC: 21 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00107 AC: 6 AN: 5584

European-Non Finnish (NFE) AF: 0.0000729 AC: 81 AN: 1111832

Other (OTH) AF: 0.000166 AC: 10 AN: 60370

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74302

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.0000655 AC: 1 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68018

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000225 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.000109

EpiControl AF: 0.000178

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	0.14
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.14	N
PhyloP100		0.46
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.049
Sift	Benign	0.036	D
Sift4G	Benign	0.20	T
Polyphen		0.053	B
Vest4		0.035
MVP		0.18
ClinPred		0.028	T
GERP RS		3.5
PromoterAI		0.0076	Neutral
Varity_R		0.12
gMVP		0.034
Mutation Taster		=96/4	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

dbSNP: rs745361366; hg19: chr11-55135676; COSMIC: COSV104406988;