dbSNP rs756430892: OLFML2B:p.Arg527Leu (chr1-161984875-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015441.3(OLFML2B):c.1580G>T(p.Arg527Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R527Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OLFML2B
NM_015441.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.21

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015441.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OLFML2B	NM_015441.3	MANE Select	c.1580G>T	p.Arg527Leu	missense	Exon 7 of 8	NP_056256.1	Q68BL8-1
OLFML2B	NM_001347700.2		c.1586G>T	p.Arg529Leu	missense	Exon 7 of 8	NP_001334629.1
OLFML2B	NM_001297713.2		c.1583G>T	p.Arg528Leu	missense	Exon 7 of 8	NP_001284642.1	F2Z3N3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OLFML2B	ENST00000294794.8	TSL:1 MANE Select	c.1580G>T	p.Arg527Leu	missense	Exon 7 of 8	ENSP00000294794.3	Q68BL8-1
OLFML2B	ENST00000367940.2	TSL:2	c.1583G>T	p.Arg528Leu	missense	Exon 7 of 8	ENSP00000356917.2	F2Z3N3
OLFML2B	ENST00000367938.1	TSL:2	c.29G>T	p.Arg10Leu	missense	Exon 1 of 2	ENSP00000356915.1	Q68BL8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251462

AF XY:

0.00

show subpopulations

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111986

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.70

MetaSVM

Uncertain

0.38

MutationAssessor

Benign

1.9

PhyloP100

3.2

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-4.7

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.014

Polyphen

0.79

Vest4

0.82

MutPred

0.44

Loss of ubiquitination at K525 (P = 0.0433)

MVP

0.91

MPC

0.59

ClinPred

0.99

GERP RS

4.3

PromoterAI

-0.036

Neutral

(source)

Varity_R

0.41

gMVP

0.78

Mutation Taster

=66/34

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over