rs11568663

Positions:

• chr13-95170507-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005845.5(ABCC4):​c.1824+25G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,505,726 control chromosomes in the GnomAD database, including 10,516 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 0.077 (630 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9886 hom.)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.1824+25G>A		intron_variant		ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.1824+25G>A		intron_variant			NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11740 AN: 152072 Hom.: 631 Cov.: 32

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0641

Gnomad FIN AF: 0.0921

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0564

GnomAD3 exomes AF: 0.0806 AC: 18337 AN: 227522 Hom.: 958 AF XY: 0.0834 AC XY: 10235 AN XY: 122692

Gnomad AFR exome AF: 0.0202

Gnomad AMR exome AF: 0.0359

Gnomad ASJ exome AF: 0.0398

Gnomad EAS exome AF: 0.000979

Gnomad SAS exome AF: 0.0695

Gnomad FIN exome AF: 0.0919

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.0804

GnomAD4 exome AF: 0.114 AC: 154665 AN: 1353534 Hom.: 9886 Cov.: 19 AF XY: 0.113 AC XY: 76383 AN XY: 675312

Gnomad4 AFR exome AF: 0.0173

Gnomad4 AMR exome AF: 0.0363

Gnomad4 ASJ exome AF: 0.0408

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.0717

Gnomad4 FIN exome AF: 0.0967

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.0939

GnomAD4 genome AF: 0.0771 AC: 11733 AN: 152192 Hom.: 630 Cov.: 32 AF XY: 0.0746 AC XY: 5551 AN XY: 74426

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.0514

Gnomad4 ASJ AF: 0.0447

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0630

Gnomad4 FIN AF: 0.0921

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.104 Hom.: 1303

Bravo AF: 0.0703

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs11568663; hg19: chr13-95822761;