chr9-122568375-C-A

Variant names:

Variant summary

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

The NM_001004454.2(OR1L8):c.103G>T(p.Val35Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,613,732 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. 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. V35G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

OR1L8
NM_001004454.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03

Publications

5 publications found

Variant links:

Genes affected

OR1L8 (HGNC:15110): (olfactory receptor family 1 subfamily L member 8) 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]

OR1L8 links:

ENSG00000234156 (HGNC:):

ENSG00000234156 links:

OR1J2 (HGNC:8209): (olfactory receptor family 1 subfamily J member 2) 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]

OR1J2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.032969296).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004454.2. 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
	OR1L8	NM_001004454.2	MANE Select	c.103G>T	p.Val35Leu	missense	Exon 5 of 5	NP_001004454.1	Q8NGR8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR1L8	ENST00000641027.1	MANE Select	c.103G>T	p.Val35Leu	missense	Exon 5 of 5	ENSP00000493411.1	Q8NGR8
ENSG00000234156	ENST00000431442.3	TSL:3	n.1363-38271C>A		intron	N/A
ENSG00000234156	ENST00000723589.1		n.1045-38271C>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000267

AC:

AN:

251386

AF XY:

0.000346

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000146

AC:

214

AN:

1461524

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

147

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33470

American (AMR)

AF:

0.000268

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00132

AC:

114

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000603

AC:

AN:

1111706

Other (OTH)

AF:

0.000248

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41516

American (AMR)

AF:

0.000654

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68010

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.000288

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.3

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.74

M_CAP

Benign

0.0022

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.11

PhyloP100

-1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

0.45

REVEL

Benign

0.051

Sift

Benign

0.090

Sift4G

Benign

0.073

Polyphen

0.0

Vest4

0.032

MutPred

0.36

Loss of catalytic residue at V35 (P = 0.1012)

MVP

0.25

MPC

0.074

ClinPred

0.90

GERP RS

3.3

Varity_R

0.041

gMVP

0.096

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over