rs5956

Variant names:

• chr7-80663133-G-A
• rs5956
• NM_001001548.3:c.573G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_001001548.3(CD36):​c.573G>A​(p.Pro191Pro) 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
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 10

  Inheritance: AR Classification: STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 910697.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001548.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD36	NM_001001548.3	MANE Select	c.573G>A	p.Pro191Pro	synonymous	Exon 6 of 15	NP_001001548.1	P16671-1
	CD36	NM_000072.3		c.573G>A	p.Pro191Pro	synonymous	Exon 6 of 14	NP_000063.2	A4D1B1
	CD36	NM_001001547.3		c.573G>A	p.Pro191Pro	synonymous	Exon 6 of 14	NP_001001547.1	P16671-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD36	ENST00000447544.7	TSL:5 MANE Select	c.573G>A	p.Pro191Pro	synonymous	Exon 6 of 15	ENSP00000415743.2	P16671-1
	CD36	ENST00000309881.11	TSL:1	c.573G>A	p.Pro191Pro	synonymous	Exon 6 of 14	ENSP00000308165.7	P16671-1
	CD36	ENST00000394788.7	TSL:1	c.573G>A	p.Pro191Pro	synonymous	Exon 6 of 14	ENSP00000378268.3	P16671-1

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

GnomAD2 exomes AF: 0.0188 AC: 4714 AN: 251244 AF XY: 0.0184

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 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

African (AFR) AF: 0.00350 AC: 117 AN: 33456

American (AMR) AF: 0.00539 AC: 241 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00881 AC: 230 AN: 26110

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39608

South Asian (SAS) AF: 0.00401 AC: 346 AN: 86254

European-Finnish (FIN) AF: 0.0528 AC: 2818 AN: 53412

Middle Eastern (MID) AF: 0.00434 AC: 25 AN: 5758

European-Non Finnish (NFE) AF: 0.0278 AC: 30914 AN: 1111284

Other (OTH) AF: 0.0179 AC: 1078 AN: 60340

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

African (AFR) AF: 0.00472 AC: 196 AN: 41540

American (AMR) AF: 0.00660 AC: 101 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00750 AC: 26 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4820

European-Finnish (FIN) AF: 0.0519 AC: 549 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0281 AC: 1908 AN: 67988

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.0227 Hom.: 140

Bravo AF: 0.0148

Asia WGS AF: 0.00289 AC: 10 AN: 3476

EpiCase AF: 0.0221

EpiControl AF: 0.0222

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	Platelet-type bleeding disorder 10 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.8
DANN	Benign	0.55
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5956; hg19: chr7-80292449;