chr7-80656534-T-C

Variant names:

• chr7-80656534-T-C
• rs3173798
• NM_001001548.3:c.121-6T>C

Variant summary

Our verdict is Benign. The variant received -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, 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, intron
• Scores: Splicing: ADA: 0.0002977
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.01
• Publications: 39 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CD36	NM_001001548.3	c.121-6T>C		splice_region_variant, intron_variant	Intron 3 of 14	ENST00000447544.7	NP_001001548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD36	ENST00000447544.7	c.121-6T>C		splice_region_variant, intron_variant	Intron 3 of 14	5	NM_001001548.3	ENSP00000415743.2

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

GnomAD2 exomes AF: 0.143 AC: 35746 AN: 250448 AF XY: 0.142

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 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

African (AFR) AF: 0.215 AC: 7181 AN: 33404

American (AMR) AF: 0.176 AC: 7838 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.0751 AC: 1960 AN: 26096

East Asian (EAS) AF: 0.425 AC: 16801 AN: 39568

South Asian (SAS) AF: 0.242 AC: 20853 AN: 86168

European-Finnish (FIN) AF: 0.0749 AC: 3996 AN: 53372

Middle Eastern (MID) AF: 0.0498 AC: 285 AN: 5722

European-Non Finnish (NFE) AF: 0.0700 AC: 77767 AN: 1110840

Other (OTH) AF: 0.120 AC: 7220 AN: 60298

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

African (AFR) AF: 0.210 AC: 8731 AN: 41506

American (AMR) AF: 0.147 AC: 2241 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3472

East Asian (EAS) AF: 0.423 AC: 2181 AN: 5152

South Asian (SAS) AF: 0.257 AC: 1242 AN: 4828

European-Finnish (FIN) AF: 0.0669 AC: 710 AN: 10614

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0711 AC: 4835 AN: 68014

Other (OTH) AF: 0.125 AC: 264 AN: 2110

Alfa AF: 0.0929 Hom.: 3999

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

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Platelet-type bleeding disorder 10 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		1.0
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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