rs5956

chr7-80663133-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_001001548.3(CD36):c.573G>A(p.Pro191=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,613,100 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.019 (52 hom., cov: 32)
  • Exomes 𝑓: 0.024 (527 hom.)
• Consequence: CD36 NM_001001548.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.528

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 7-80663133-G-A is Benign according to our data. Variant chr7-80663133-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 910697.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=-0.528 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0186 (2834/152158) while in subpopulation NFE AF= 0.0281 (1908/67988). AF 95% confidence interval is 0.027. There are 52 homozygotes in gnomad4. There are 1418 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD36	NM_001001548.3	c.573G>A	p.Pro191=	synonymous_variant	6/15	ENST00000447544.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD36	ENST00000447544.7	c.573G>A	p.Pro191=	synonymous_variant	6/15	5	NM_001001548.3	P1

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2836 AN: 152040 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00476

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0281

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0188 AC: 4714 AN: 251244 Hom.: 74 AF XY: 0.0184 AC XY: 2500 AN XY: 135790

Gnomad AFR exome AF: 0.00461

Gnomad AMR exome AF: 0.00500

Gnomad ASJ exome AF: 0.00784

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00379

Gnomad FIN exome AF: 0.0532

Gnomad NFE exome AF: 0.0264

Gnomad OTH exome AF: 0.0196

GnomAD4 exome AF: 0.0245 AC: 35771 AN: 1460942 Hom.: 527 Cov.: 31 AF XY: 0.0240 AC XY: 17428 AN XY: 726810

Gnomad4 AFR exome AF: 0.00350

Gnomad4 AMR exome AF: 0.00539

Gnomad4 ASJ exome AF: 0.00881

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.00401

Gnomad4 FIN exome AF: 0.0528

Gnomad4 NFE exome AF: 0.0278

Gnomad4 OTH exome AF: 0.0179

GnomAD4 genome AF: 0.0186 AC: 2834 AN: 152158 Hom.: 52 Cov.: 32 AF XY: 0.0191 AC XY: 1418 AN XY: 74368

Gnomad4 AFR AF: 0.00472

Gnomad4 AMR AF: 0.00660

Gnomad4 ASJ AF: 0.00750

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.0519

Gnomad4 NFE AF: 0.0281

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0229 Hom.: 56

Bravo AF: 0.0148

Asia WGS AF: 0.00289 AC: 10 AN: 3476

EpiCase AF: 0.0221

EpiControl AF: 0.0222

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Platelet-type bleeding disorder 10 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	7.8
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

Other links and lift over

dbSNP: rs5956; hg19: chr7-80292449;