rs3211938

Variant names:

• chr7-80671133-T-G
• rs3211938
• NM_001001548.3:c.975T>G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 8P and 9B. PVS1 BP6 BA1

The NM_001001548.3(CD36):​c.975T>G​(p.Tyr325*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00458 in 1,612,872 control chromosomes in the GnomAD database, including 414 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.025 (194 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (220 hom.)
• Consequence: CD36 NM_001001548.3 stop_gained
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1 U:1 B:1 O:1
• Conservation: PhyloP100: 0.457

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 Likely_benign. Variant got -1 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• BP6: Variant 7-80671133-T-G is Benign according to our data. Variant chr7-80671133-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 13536.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD36	NM_001001548.3	c.975T>G	p.Tyr325*	stop_gained	Exon 10 of 15	ENST00000447544.7	NP_001001548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD36	ENST00000447544.7	c.975T>G	p.Tyr325*	stop_gained	Exon 10 of 15	5	NM_001001548.3	ENSP00000415743.2

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3739 AN: 152178 Hom.: 194 Cov.: 33

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00957

GnomAD3 exomes AF: 0.00617 AC: 1545 AN: 250362 Hom.: 78 AF XY: 0.00437 AC XY: 592 AN XY: 135332

Gnomad AFR exome AF: 0.0885

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00249 AC: 3639 AN: 1460576 Hom.: 220 Cov.: 29 AF XY: 0.00218 AC XY: 1585 AN XY: 726654

Gnomad4 AFR exome AF: 0.0946

Gnomad4 AMR exome AF: 0.00309

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00471

GnomAD4 genome AF: 0.0246 AC: 3740 AN: 152296 Hom.: 194 Cov.: 33 AF XY: 0.0233 AC XY: 1734 AN XY: 74470

Gnomad4 AFR AF: 0.0872

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00520 Hom.: 60

Bravo AF: 0.0270

ESP6500AA AF: 0.0819 AC: 361

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00788 AC: 956

Asia WGS AF: 0.00520 AC: 18 AN: 3476

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Uncertain:1 Benign:1 Other:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Platelet-type bleeding disorder 10 Pathogenic:1 Uncertain:1

Jun 01, 2008

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 specified Benign:1

May 09, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Malaria, cerebral, susceptibility to Other:1

Jun 01, 2008

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Pathogenic	0.49
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.82	D
Vest4		0.85
GERP RS		-0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3211938; hg19: chr7-80300449;