rs1049654

chr7-80646139-A-Cchr7-80646139-A-Gchr7-80646139-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001001548.3(CD36):c.-132A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 153,858 control chromosomes in the GnomAD database, including 19,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19285 hom., cov: 32)
  • Exomes 𝑓: 0.49 (236 hom.)
• Consequence: CD36 NM_001001548.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.283

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=-0.68).
• BP6: Variant 7-80646139-A-C is Benign according to our data. Variant chr7-80646139-A-C is described in ClinVar as [Benign]. Clinvar id is 360748.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD36	NM_001001548.3	c.-132A>C		5_prime_UTR_variant	2/15	ENST00000447544.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD36	ENST00000447544.7	c.-132A>C		5_prime_UTR_variant	2/15	5	NM_001001548.3	P1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75478 AN: 151874 Hom.: 19273 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.488 AC: 910 AN: 1866 Hom.: 236 Cov.: 0 AF XY: 0.475 AC XY: 478 AN XY: 1006

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.515

GnomAD4 genome AF: 0.497 AC: 75519 AN: 151992 Hom.: 19285 Cov.: 32 AF XY: 0.493 AC XY: 36615 AN XY: 74264

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.516

Alfa AF: 0.533 Hom.: 20184

Bravo AF: 0.501

Asia WGS AF: 0.304 AC: 1060 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Platelet-type bleeding disorder 10 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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	-0.68
Cadd	Benign	8.4
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1049654; hg19: chr7-80275455;