rs2487566

Variant names:

• chr13-95193018-G-A
• rs2487566
• NM_005845.5:c.1263+1818C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-95193018-G-A
• chr13-95193018-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005845.5(ABCC4):​c.1263+1818C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,154 control chromosomes in the GnomAD database, including 19,649 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (19649 hom., cov: 34)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 8 publications found

Genes affected

ABCC4 (HGNC:55): (ATP binding cassette subfamily C member 4 (PEL blood group)) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This family member plays a role in cellular detoxification as a pump for its substrate, organic anions. It may also function in prostaglandin-mediated cAMP signaling in ciliogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

ABCC4 Gene-Disease associations (from GenCC):

• qualitative platelet defect

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005845.5. 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
	ABCC4	NM_005845.5	MANE Select	c.1263+1818C>T		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.1263+1818C>T		intron	N/A	NP_001288758.1
	ABCC4	NM_001105515.3		c.1263+1818C>T		intron	N/A	NP_001098985.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.1263+1818C>T		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.1263+1818C>T		intron	N/A	ENSP00000487081.1
	ABCC4	ENST00000967420.1		c.1263+1818C>T		intron	N/A	ENSP00000637479.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77268 AN: 152036 Hom.: 19642 Cov.: 34

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.505

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.508 AC: 77315 AN: 152154 Hom.: 19649 Cov.: 34 AF XY: 0.504 AC XY: 37456 AN XY: 74386

African (AFR) AF: 0.521 AC: 21603 AN: 41496

American (AMR) AF: 0.518 AC: 7927 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1680 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2197 AN: 5182

South Asian (SAS) AF: 0.425 AC: 2049 AN: 4824

European-Finnish (FIN) AF: 0.498 AC: 5272 AN: 10590

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 35027 AN: 67984

Other (OTH) AF: 0.501 AC: 1059 AN: 2112

Alfa AF: 0.515 Hom.: 60977

Bravo AF: 0.513

Asia WGS AF: 0.448 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.5
DANN	Benign	0.43
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2487566; hg19: chr13-95845272;