Variant chr1-161997828-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015441.3(OLFML2B):c.1471A>G(p.Ile491Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000158 in 1,459,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

OLFML2B
NM_015441.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

Variant links:

Genes affected

OLFML2B (HGNC:24558): (olfactomedin like 2B) This gene encodes an olfactomedin domain-containing protein. Most olfactomedin domain-containing proteins are secreted glycoproteins. [provided by RefSeq, Dec 2016]

OLFML2B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08740789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OLFML2B	NM_015441.3 linkuse as main transcript	c.1471A>G	p.Ile491Val	missense_variant	6/8	ENST00000294794.8
OLFML2B	NM_001347700.2 linkuse as main transcript	c.1477A>G	p.Ile493Val	missense_variant	6/8
OLFML2B	NM_001297713.2 linkuse as main transcript	c.1474A>G	p.Ile492Val	missense_variant	6/8
OLFML2B	XM_011509398.3 linkuse as main transcript	c.751A>G	p.Ile251Val	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFML2B	ENST00000294794.8 linkuse as main transcript	c.1471A>G	p.Ile491Val	missense_variant	6/8	1	NM_015441.3	P3	Q68BL8-1
OLFML2B	ENST00000367940.2 linkuse as main transcript	c.1474A>G	p.Ile492Val	missense_variant	6/8	2		A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000765

AC:

AN:

248268

Hom.:

AF XY:

0.0000745

AC XY:

AN XY:

134236

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1459376

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725658

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000493

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.1471A>G (p.I491V) alteration is located in exon 6 (coding exon 6) of the OLFML2B gene. This alteration results from a A to G substitution at nucleotide position 1471, causing the isoleucine (I) at amino acid position 491 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.0021

T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.028

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.087

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.80

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.13

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.033

D;D

Sift4G

Benign

0.81

T;T

Polyphen

0.022

B;B

Vest4

0.47

MutPred

0.36

.;Gain of helix (P = 0.0325);

MVP

0.46

MPC

0.22

ClinPred

0.13

GERP RS

4.5

Varity_R

0.070

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over