rs4148544

Variant names:

• chr13-95028131-C-T
• rs4148544
• NM_005845.5:c.3871-6449G>A

Variant summary

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

The NM_005845.5(ABCC4):​c.3871-6449G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,958 control chromosomes in the GnomAD database, including 8,579 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 0.33 (8579 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.3871-6449G>A		intron_variant	Intron 30 of 30	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.3730-6449G>A		intron_variant	Intron 29 of 29		NP_001288758.1
ABCC4	XM_047430034.1	c.3742-6449G>A		intron_variant	Intron 30 of 30		XP_047285990.1
ABCC4	XM_047430035.1	c.3322-6449G>A		intron_variant	Intron 27 of 27		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.3871-6449G>A		intron_variant	Intron 30 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50502 AN: 151840 Hom.: 8573 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.332 AC: 50523 AN: 151958 Hom.: 8579 Cov.: 32 AF XY: 0.333 AC XY: 24722 AN XY: 74266

African (AFR) AF: 0.264 AC: 10942 AN: 41446

American (AMR) AF: 0.381 AC: 5815 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1104 AN: 3470

East Asian (EAS) AF: 0.505 AC: 2615 AN: 5176

South Asian (SAS) AF: 0.452 AC: 2175 AN: 4816

European-Finnish (FIN) AF: 0.298 AC: 3144 AN: 10542

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.348 AC: 23637 AN: 67936

Other (OTH) AF: 0.345 AC: 728 AN: 2110

Alfa AF: 0.345 Hom.: 15487

Bravo AF: 0.337

Asia WGS AF: 0.466 AC: 1622 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.2
DANN	Benign	0.62
PhyloP100		-0.17
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: rs4148544; hg19: chr13-95680385;