rs1049654

Variant names:

• chr7-80646139-A-C
• rs1049654
• NM_001001548.3:c.-132A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-80646139-A-C
• chr7-80646139-A-G
• chr7-80646139-A-T

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.-132A>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 0.497 in 153,858 control chromosomes in the GnomAD database, including 19,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19285 hom., cov: 32)
  • Exomes 𝑓: 0.49 (236 hom.)
• Consequence: CD36 NM_001001548.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.283
• Publications: 24 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=-0.68).
• BP6: Variant 7-80646139-A-C is Benign according to our data. Variant chr7-80646139-A-C is described in ClinVar as Benign. ClinVar VariationId is 360748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD36	NM_001001548.3	c.-132A>C		5_prime_UTR_variant	Exon 2 of 15	ENST00000447544.7	NP_001001548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD36	ENST00000447544.7	c.-132A>C		5_prime_UTR_variant	Exon 2 of 15	5	NM_001001548.3	ENSP00000415743.2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75478 AN: 151874 Hom.: 19273 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.488 AC: 910 AN: 1866 Hom.: 236 Cov.: 0 AF XY: 0.475 AC XY: 478 AN XY: 1006

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.488 AC: 210 AN: 430

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 3 AN: 8

East Asian (EAS) AF: 0.190 AC: 8 AN: 42

South Asian (SAS) AF: 0.216 AC: 38 AN: 176

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.540 AC: 615 AN: 1138

Other (OTH) AF: 0.515 AC: 34 AN: 66

GnomAD4 genome AF: 0.497 AC: 75519 AN: 151992 Hom.: 19285 Cov.: 32 AF XY: 0.493 AC XY: 36615 AN XY: 74264

African (AFR) AF: 0.421 AC: 17477 AN: 41476

American (AMR) AF: 0.528 AC: 8048 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1991 AN: 3472

East Asian (EAS) AF: 0.322 AC: 1658 AN: 5142

South Asian (SAS) AF: 0.299 AC: 1439 AN: 4818

European-Finnish (FIN) AF: 0.532 AC: 5598 AN: 10524

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37597 AN: 67986

Other (OTH) AF: 0.516 AC: 1091 AN: 2116

Alfa AF: 0.532 Hom.: 26752

Bravo AF: 0.501

Asia WGS AF: 0.304 AC: 1060 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

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.4
DANN	Benign	0.86
PhyloP100		0.28
PromoterAI		-0.10	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1049654; hg19: chr7-80275455;