NM_001001548.3:c.282-10A>G

Variant names:

• chr7-80661053-A-G
• rs3211892
• NM_001001548.3:c.282-10A>G

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.282-10A>G variant causes a 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 intron
• Scores: Splicing: ADA: 0.00001424
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.65
• Publications: 26 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

ENSG00000298725 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 360754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD36	NM_001001548.3	c.282-10A>G		intron_variant	Intron 4 of 14	ENST00000447544.7	NP_001001548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD36	ENST00000447544.7	c.282-10A>G		intron_variant	Intron 4 of 14	5	NM_001001548.3	ENSP00000415743.2

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

GnomAD2 exomes AF: 0.968 AC: 242906 AN: 250876 AF XY: 0.972

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 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

African (AFR) AF: 0.784 AC: 26092 AN: 33276

American (AMR) AF: 0.976 AC: 43646 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 25096 AN: 26090

East Asian (EAS) AF: 1.00 AC: 39599 AN: 39600

South Asian (SAS) AF: 0.996 AC: 85719 AN: 86106

European-Finnish (FIN) AF: 0.980 AC: 52333 AN: 53402

Middle Eastern (MID) AF: 0.973 AC: 5585 AN: 5742

European-Non Finnish (NFE) AF: 0.978 AC: 1080239 AN: 1104566

Other (OTH) AF: 0.967 AC: 58113 AN: 60118

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

African (AFR) AF: 0.797 AC: 33051 AN: 41486

American (AMR) AF: 0.962 AC: 14719 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3350 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5157 AN: 5158

South Asian (SAS) AF: 0.995 AC: 4804 AN: 4826

European-Finnish (FIN) AF: 0.981 AC: 10419 AN: 10616

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.977 AC: 66491 AN: 68038

Other (OTH) AF: 0.946 AC: 1995 AN: 2108

Alfa AF: 0.944 Hom.: 40298

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

Mar 03, 2015

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 12, 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	-0.85
CADD	Benign	0.94
DANN	Benign	0.41
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3211892; hg19: chr7-80290369;