rs3173798

Positions:

• chr7-80656534-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001001548.3(CD36):​c.121-6T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,612,296 control chromosomes in the GnomAD database, including 13,527 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2027 hom., cov: 32)
  • Exomes 𝑓: 0.099 (11500 hom.)
• Consequence: CD36 NM_001001548.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0002977
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.01

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-80656534-T-C is Benign according to our data. Variant chr7-80656534-T-C is described in ClinVar as [Benign]. Clinvar id is 360750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD36	NM_001001548.3	c.121-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000447544.7	NP_001001548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD36	ENST00000447544.7	c.121-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001001548.3	ENSP00000415743	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20451 AN: 152070 Hom.: 2020 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.0669

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.143 AC: 35746 AN: 250448 Hom.: 3953 AF XY: 0.142 AC XY: 19167 AN XY: 135384

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.0769

Gnomad EAS exome AF: 0.420

Gnomad SAS exome AF: 0.244

Gnomad FIN exome AF: 0.0725

Gnomad NFE exome AF: 0.0706

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.0986 AC: 143901 AN: 1460108 Hom.: 11500 Cov.: 31 AF XY: 0.102 AC XY: 73786 AN XY: 726438

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.0751

Gnomad4 EAS exome AF: 0.425

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.0749

Gnomad4 NFE exome AF: 0.0700

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.135 AC: 20483 AN: 152188 Hom.: 2027 Cov.: 32 AF XY: 0.137 AC XY: 10218 AN XY: 74416

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.0669

Gnomad4 NFE AF: 0.0711

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0856 Hom.: 1621

Bravo AF: 0.139

Asia WGS AF: 0.343 AC: 1189 AN: 3478

EpiCase AF: 0.0672

EpiControl AF: 0.0681

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Platelet-type bleeding disorder 10 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.1
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00030
dbscSNV1_RF	Benign	0.016
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

LitVar

Other links and lift over

dbSNP: rs3173798; hg19: chr7-80285850; COSMIC: COSV59212036;