7-80602188-G-C

Position:

• chr7-80602188-G-C

Variant summary

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

The ENST00000309881.11(CD36):​c.-375G>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 0.528 in 151,940 control chromosomes in the GnomAD database, including 22,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (22221 hom., cov: 32)
  • Exomes 𝑓: 0.39 (0 hom.)
• Consequence: CD36 ENST00000309881.11 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0130

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=-0.94).
• BP6: Variant 7-80602188-G-C is Benign according to our data. Variant chr7-80602188-G-C is described in ClinVar as [Benign]. Clinvar id is 360740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD36	NM_001001547.3			upstream_gene_variant			NP_001001547.1
CD36	NM_001289911.2			upstream_gene_variant			NP_001276840.1
CD36	NM_001371074.1			upstream_gene_variant			NP_001358003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD36	ENST00000309881.11	c.-375G>C		5_prime_UTR_variant	1/14	1		ENSP00000308165	P1
CD36	ENST00000435819.5	c.-183-43900G>C		intron_variant		2		ENSP00000399421	P1
CD36	ENST00000480599.6	n.39G>C		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80118 AN: 151804 Hom.: 22183 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.389 AC: 7 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.333 AC XY: 4 AN XY: 12

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.528 AC: 80205 AN: 151922 Hom.: 22221 Cov.: 32 AF XY: 0.531 AC XY: 39426 AN XY: 74240

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.500

Alfa AF: 0.467 Hom.: 9643

Bravo AF: 0.525

Asia WGS AF: 0.711 AC: 2470 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.1
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1194182; hg19: chr7-80231504;