rs550565800

Variant names:

• chr7-80673381-ATATTGTGCCTAT-A
• rs550565800
• NM_001001548.3:c.1228_1239delATTGTGCCTATT

Your query was ambiguous. Multiple possible variants found:

• chr7-80673381-ATATTGTGCCTAT-A
• chr7-80673381-ATATTGTGCCTAT-ATATTGTGCCTATTGTGCCTAT

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PM4 PP5_Very_Strong

The NM_001001548.3(CD36):​c.1228_1239delATTGTGCCTATT​(p.Ile410_Ile413del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,566,970 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: CD36 NM_001001548.3 conservative_inframe_deletion
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:6
• Conservation: PhyloP100: 2.64
• Publications: 3 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001001548.3.
• PP5: Variant 7-80673381-ATATTGTGCCTAT-A is Pathogenic according to our data. Variant chr7-80673381-ATATTGTGCCTAT-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 225310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001548.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD36	NM_001001548.3	MANE Select	c.1228_1239delATTGTGCCTATT	p.Ile410_Ile413del	conservative_inframe_deletion	Exon 13 of 15	NP_001001548.1	P16671-1
	CD36	NM_000072.3		c.1228_1239delATTGTGCCTATT	p.Ile410_Ile413del	conservative_inframe_deletion	Exon 13 of 14	NP_000063.2	A4D1B1
	CD36	NM_001001547.3		c.1228_1239delATTGTGCCTATT	p.Ile410_Ile413del	conservative_inframe_deletion	Exon 13 of 14	NP_001001547.1	P16671-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD36	ENST00000447544.7	TSL:5 MANE Select	c.1228_1239delATTGTGCCTATT	p.Ile410_Ile413del	conservative_inframe_deletion	Exon 13 of 15	ENSP00000415743.2	P16671-1
	CD36	ENST00000309881.11	TSL:1	c.1228_1239delATTGTGCCTATT	p.Ile410_Ile413del	conservative_inframe_deletion	Exon 13 of 14	ENSP00000308165.7	P16671-1
	CD36	ENST00000394788.7	TSL:1	c.1228_1239delATTGTGCCTATT	p.Ile410_Ile413del	conservative_inframe_deletion	Exon 13 of 14	ENSP00000378268.3	P16671-1

Frequencies

GnomAD3 genomes AF: 0.000356 AC: 54 AN: 151878 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000784 AC: 196 AN: 250154 AF XY: 0.000688

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0107

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000112 AC: 158 AN: 1414974 Hom.: 0 AF XY: 0.000116 AC XY: 82 AN XY: 706964

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32482

American (AMR) AF: 0.00 AC: 0 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25714

East Asian (EAS) AF: 0.00393 AC: 154 AN: 39142

South Asian (SAS) AF: 0.00 AC: 0 AN: 85188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1070082

Other (OTH) AF: 0.0000511 AC: 3 AN: 58740

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000355 AC: 54 AN: 151996 Hom.: 0 Cov.: 32 AF XY: 0.000350 AC XY: 26 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67784

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000457

ClinVar

ClinVar submissions

Significance: Pathogenic/Likely pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
5	-	-	Platelet-type bleeding disorder 10 (5)
1	-	-	CD36-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=0/200	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs550565800; hg19: chr7-80302697; COSMIC: COSV59211338;