13-95241533-C-G

Variant names:

• chr13-95241533-C-G
• rs4283094
• NM_005845.5:c.306+5442G>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.306+5442G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,840 control chromosomes in the GnomAD database, including 22,739 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 0.54 (22739 hom., cov: 31)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.306+5442G>C		intron_variant	Intron 3 of 30	ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.306+5442G>C		intron_variant	Intron 3 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81509 AN: 151722 Hom.: 22711 Cov.: 31

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.537 AC: 81589 AN: 151840 Hom.: 22739 Cov.: 31 AF XY: 0.535 AC XY: 39721 AN XY: 74228

African (AFR) AF: 0.671 AC: 27794 AN: 41422

American (AMR) AF: 0.479 AC: 7313 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1512 AN: 3468

East Asian (EAS) AF: 0.476 AC: 2453 AN: 5148

South Asian (SAS) AF: 0.491 AC: 2362 AN: 4814

European-Finnish (FIN) AF: 0.480 AC: 5058 AN: 10546

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33696 AN: 67884

Other (OTH) AF: 0.509 AC: 1075 AN: 2112

Alfa AF: 0.374 Hom.: 931

Bravo AF: 0.541

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.35
PhyloP100		-0.21
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: rs4283094; hg19: chr13-95893787;