Variant 1-161984259-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP4_StrongBS1_SupportingBS2

The NM_015441.3(OLFML2B):c.1669T>C(p.Tyr557His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000633 in 1,520,824 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 9 hom. )

Consequence

OLFML2B
NM_015441.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.15

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_noAF, Cadd, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationAssessor, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.023408681).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000558 (85/152352) while in subpopulation SAS AF= 0.00539 (26/4826). AF 95% confidence interval is 0.00378. There are 0 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFML2B	NM_015441.3 linkuse as main transcript	c.1669T>C	p.Tyr557His	missense_variant	8/8	ENST00000294794.8	NP_056256.1	Q68BL8-1
OLFML2B	NM_001347700.2 linkuse as main transcript	c.1675T>C	p.Tyr559His	missense_variant	8/8		NP_001334629.1
OLFML2B	NM_001297713.2 linkuse as main transcript	c.1672T>C	p.Tyr558His	missense_variant	8/8		NP_001284642.1	Q68BL8F2Z3N3B4DWE8
OLFML2B	XM_011509398.3 linkuse as main transcript	c.949T>C	p.Tyr317His	missense_variant	5/5		XP_011507700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OLFML2B	ENST00000294794.8 linkuse as main transcript	c.1669T>C	p.Tyr557His	missense_variant	8/8	1	NM_015441.3	ENSP00000294794.3	Q68BL8-1
OLFML2B	ENST00000367940.2 linkuse as main transcript	c.1672T>C	p.Tyr558His	missense_variant	8/8	2		ENSP00000356917.2	F2Z3N3
OLFML2B	ENST00000367938.1 linkuse as main transcript	c.118T>C	p.Tyr40His	missense_variant	2/2	2		ENSP00000356915.1	Q68BL8-2

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000824

AC:

143

AN:

173512

Hom.:

AF XY:

0.00113

AC XY:

103

AN XY:

91164

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000563

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00682

Gnomad FIN exome

AF:

0.000175

Gnomad NFE exome

AF:

0.000304

Gnomad OTH exome

AF:

0.00100

GnomAD4 exome

AF:

0.000642

AC:

878

AN:

1368472

Hom.:

Cov.:

AF XY:

0.000898

AC XY:

602

AN XY:

670296

show subpopulations

Gnomad4 AFR exome

AF:

0.0000659

Gnomad4 AMR exome

AF:

0.000502

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00836

Gnomad4 FIN exome

AF:

0.0000604

Gnomad4 NFE exome

AF:

0.000169

Gnomad4 OTH exome

AF:

0.000853

GnomAD4 genome

AF:

0.000558

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000684

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000330

Hom.:

Bravo

AF:

0.000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000883

AC:

105

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

OLFML2B: PP3 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;D;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.023

T;T;T

MetaSVM

Uncertain

0.48

MutationAssessor

Benign

1.2

L;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Pathogenic

0.84

Sift

Benign

0.087

T;T;T

Sift4G

Benign

0.072

T;T;T

Polyphen

0.83

P;D;.

Vest4

0.95

MVP

0.87

MPC

0.63

ClinPred

0.11

GERP RS

5.2

Varity_R

0.35

gMVP

0.75

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

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