7-80661053-A-G

Position:

• chr7-80661053-A-G

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.282-10A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,605,826 control chromosomes in the GnomAD database, including 756,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66006 hom., cov: 32)
  • Exomes 𝑓: 0.97 (690813 hom.)
• Consequence: CD36 NM_001001548.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001424
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.65

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=-0.85).
• BP6: Variant 7-80661053-A-G is Benign according to our data. Variant chr7-80661053-A-G is described in ClinVar as [Benign]. Clinvar id is 360754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-80661053-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD36	NM_001001548.3	c.282-10A>G		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.282-10A>G		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001001548.3	ENSP00000415743	P1

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141108 AN: 152092 Hom.: 65985 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.981

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.977

Gnomad OTH AF: 0.946

GnomAD3 exomes AF: 0.968 AC: 242906 AN: 250876 Hom.: 117888 AF XY: 0.972 AC XY: 131717 AN XY: 135564

Gnomad AFR exome AF: 0.792

Gnomad AMR exome AF: 0.978

Gnomad ASJ exome AF: 0.960

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.996

Gnomad FIN exome AF: 0.980

Gnomad NFE exome AF: 0.976

Gnomad OTH exome AF: 0.974

GnomAD4 exome AF: 0.974 AC: 1416422 AN: 1453616 Hom.: 690813 Cov.: 31 AF XY: 0.976 AC XY: 706224 AN XY: 723914

Gnomad4 AFR exome AF: 0.784

Gnomad4 AMR exome AF: 0.976

Gnomad4 ASJ exome AF: 0.962

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.996

Gnomad4 FIN exome AF: 0.980

Gnomad4 NFE exome AF: 0.978

Gnomad4 OTH exome AF: 0.967

GnomAD4 genome AF: 0.928 AC: 141181 AN: 152210 Hom.: 66006 Cov.: 32 AF XY: 0.930 AC XY: 69170 AN XY: 74398

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.962

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.995

Gnomad4 FIN AF: 0.981

Gnomad4 NFE AF: 0.977

Gnomad4 OTH AF: 0.946

Alfa AF: 0.944 Hom.: 34800

Bravo AF: 0.920

Asia WGS AF: 0.980 AC: 3408 AN: 3478

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	Mar 03, 2015	- -
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 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	-0.85
CADD	Benign	0.94
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0
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: rs3211892; hg19: chr7-80290369;