11-55638779-C-T

Variant names:

• chr11-55638779-C-T
• rs139375531
• NM_001405919.1:c.422C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001405919.1(OR4P4):​c.422C>T​(p.Thr141Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000402 in 1,492,430 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T141K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000030 (1 hom.)
• Consequence: OR4P4 NM_001405919.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 1 publications found

Genes affected

OR4P4 (HGNC:15180): (olfactory receptor family 4 subfamily P member 4) 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042462498).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405919.1. 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
	OR4P4	NM_001405919.1	MANE Select	c.422C>T	p.Thr141Ile	missense	Exon 2 of 2	NP_001392848.1	Q8NGL7
	OR4P4	NM_001004124.2		c.422C>T	p.Thr141Ile	missense	Exon 1 of 1	NP_001004124.1	Q8NGL7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4P4	ENST00000641760.1	MANE Select	c.422C>T	p.Thr141Ile	missense	Exon 2 of 2	ENSP00000493384.1	Q8NGL7

Frequencies

GnomAD3 genomes AF: 0.00000720 AC: 1 AN: 138886 Hom.: 0 Cov.: 25

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: 0.00347

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000442 AC: 1 AN: 226376 AF XY: 0.00000815

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000296 AC: 4 AN: 1353458 Hom.: 1 Cov.: 31 AF XY: 0.00000594 AC XY: 4 AN XY: 673142

African (AFR) AF: 0.00 AC: 0 AN: 32906

American (AMR) AF: 0.00 AC: 0 AN: 37178

Ashkenazi Jewish (ASJ) AF: 0.0000412 AC: 1 AN: 24258

East Asian (EAS) AF: 0.00 AC: 0 AN: 34558

South Asian (SAS) AF: 0.00 AC: 0 AN: 80452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5030

European-Non Finnish (NFE) AF: 0.00000290 AC: 3 AN: 1035224

Other (OTH) AF: 0.00 AC: 0 AN: 55924

GnomAD4 genome AF: 0.0000144 AC: 2 AN: 138972 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 67504

African (AFR) AF: 0.00 AC: 0 AN: 40054

American (AMR) AF: 0.00 AC: 0 AN: 12804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3226

East Asian (EAS) AF: 0.00 AC: 0 AN: 4212

South Asian (SAS) AF: 0.00 AC: 0 AN: 4280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9038

Middle Eastern (MID) AF: 0.00752 AC: 2 AN: 266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62418

Other (OTH) AF: 0.00 AC: 0 AN: 1852

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000322 AC: 1 AN: 3124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.21
DANN	Benign	0.55
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.095	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.61	N
PhyloP100		-2.3
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.014
Sift	Benign	0.32	T
Sift4G	Benign	0.35	T
Polyphen		0.0020	B
Vest4		0.19
MutPred		0.21		Loss of catalytic residue at T141 (P = 0.0059)
MVP		0.25
MPC		0.020
ClinPred		0.075	T
GERP RS		-3.3
Varity_R		0.035
gMVP		0.041
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

dbSNP: rs139375531; hg19: chr11-55406255;