rs4148475

Variant names:

• chr13-95201320-T-A
• rs4148475
• NM_005845.5:c.1161+5212A>T

Variant summary

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

The NM_005845.5(ABCC4):​c.1161+5212A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 152,214 control chromosomes in the GnomAD database, including 823 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 0.087 (823 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.1161+5212A>T		intron_variant	Intron 8 of 30	ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.1161+5212A>T		intron_variant	Intron 8 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13307 AN: 152096 Hom.: 822 Cov.: 32

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0897

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.0995

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

GnomAD4 genome AF: 0.0874 AC: 13304 AN: 152214 Hom.: 823 Cov.: 32 AF XY: 0.0916 AC XY: 6814 AN XY: 74418

African (AFR) AF: 0.0202 AC: 838 AN: 41542

American (AMR) AF: 0.181 AC: 2764 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3470

East Asian (EAS) AF: 0.189 AC: 976 AN: 5172

South Asian (SAS) AF: 0.120 AC: 577 AN: 4820

European-Finnish (FIN) AF: 0.0897 AC: 950 AN: 10590

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0920 AC: 6255 AN: 68020

Other (OTH) AF: 0.0975 AC: 206 AN: 2112

Alfa AF: 0.0848 Hom.: 104

Bravo AF: 0.0946

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.77
PhyloP100		-0.37
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: rs4148475; hg19: chr13-95853574;