rs121918035

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_001001548.3(CD36):c.1237A>C(p.Ile413Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,569,976 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CD36
NM_001001548.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.117

Variant links:

Genes affected

CD36 (HGNC:1663): (CD36 molecule (CD36 blood group)) The protein encoded by this gene is the fourth major glycoprotein of the platelet surface and serves as a receptor for thrombospondin in platelets and various cell lines. Since thrombospondins are widely distributed proteins involved in a variety of adhesive processes, this protein may have important functions as a cell adhesion molecule. It binds to collagen, thrombospondin, anionic phospholipids and oxidized LDL. It directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes and it binds long chain fatty acids and may function in the transport and/or as a regulator of fatty acid transport. Mutations in this gene cause platelet glycoprotein deficiency. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2014]

CD36 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 7-80673392-A-C is Pathogenic according to our data. Variant chr7-80673392-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 13541.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD36	NM_001001548.3 linkuse as main transcript	c.1237A>C	p.Ile413Leu	missense_variant	13/15	ENST00000447544.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD36	ENST00000447544.7 linkuse as main transcript	c.1237A>C	p.Ile413Leu	missense_variant	13/15	5	NM_001001548.3	P1	P16671-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151758

Hom.:

Cov.:

show subpopulations

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:

0.00968

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250228

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135300

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000120

AC:

AN:

1418100

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

708278

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000180

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000466

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151876

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.000474

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Platelet-type bleeding disorder 10

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.13

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.093

T;T;.;.;.;T;T;T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.54

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.51

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

L;L;.;.;.;L;L;L;.

MutationTaster

Benign

0.77

A;A;A;A;A;A;A;A;A

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.6

N;N;N;N;N;N;N;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.10

T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.13

T;T;T;D;T;T;T;T;T

Polyphen

0.017

B;B;.;.;.;B;B;B;.

Vest4

0.79

MutPred

0.84

Gain of catalytic residue at I413 (P = 6e-04);Gain of catalytic residue at I413 (P = 6e-04);.;.;.;Gain of catalytic residue at I413 (P = 6e-04);Gain of catalytic residue at I413 (P = 6e-04);Gain of catalytic residue at I413 (P = 6e-04);Gain of catalytic residue at I413 (P = 6e-04);

MVP

0.27

MPC

0.00037

ClinPred

0.087

GERP RS

0.47

Varity_R

0.40

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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