rs870004

Variant names:

• chr13-95265809-G-A
• rs870004
• NM_005845.5:c.75-18056C>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.75-18056C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,994 control chromosomes in the GnomAD database, including 4,525 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 0.23 (4525 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.75-18056C>T		intron_variant	Intron 1 of 30	ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.75-18056C>T		intron_variant	Intron 1 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34221 AN: 151876 Hom.: 4513 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.225 AC: 34271 AN: 151994 Hom.: 4525 Cov.: 32 AF XY: 0.221 AC XY: 16393 AN XY: 74280

African (AFR) AF: 0.365 AC: 15100 AN: 41414

American (AMR) AF: 0.209 AC: 3191 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 766 AN: 3468

East Asian (EAS) AF: 0.167 AC: 866 AN: 5176

South Asian (SAS) AF: 0.133 AC: 642 AN: 4814

European-Finnish (FIN) AF: 0.147 AC: 1553 AN: 10552

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11484 AN: 67994

Other (OTH) AF: 0.207 AC: 435 AN: 2102

Alfa AF: 0.191 Hom.: 9918

Bravo AF: 0.234

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.37
DANN	Benign	0.55
PhyloP100		-0.75
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: rs870004; hg19: chr13-95918063;