chr13-95170507-C-T

Variant names:

• chr13-95170507-C-T
• rs11568663
• NM_005845.5:c.1824+25G>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.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
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005845.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.1824+25G>A		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.1824+25G>A		intron	N/A	NP_001288758.1
	ABCC4	NM_001105515.3		c.1824+25G>A		intron	N/A	NP_001098985.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.1824+25G>A		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.1824+25G>A		intron	N/A	ENSP00000487081.1
	ABCC4	ENST00000967420.1		c.1824+25G>A		intron	N/A	ENSP00000637479.1

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

GnomAD2 exomes AF: 0.0806 AC: 18337 AN: 227522 AF XY: 0.0834

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 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

African (AFR) AF: 0.0173 AC: 539 AN: 31084

American (AMR) AF: 0.0363 AC: 1463 AN: 40252

Ashkenazi Jewish (ASJ) AF: 0.0408 AC: 1017 AN: 24910

East Asian (EAS) AF: 0.00101 AC: 39 AN: 38756

South Asian (SAS) AF: 0.0717 AC: 5731 AN: 79880

European-Finnish (FIN) AF: 0.0967 AC: 4980 AN: 51486

Middle Eastern (MID) AF: 0.0420 AC: 232 AN: 5520

European-Non Finnish (NFE) AF: 0.132 AC: 135348 AN: 1025050

Other (OTH) AF: 0.0939 AC: 5316 AN: 56596

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

African (AFR) AF: 0.0230 AC: 954 AN: 41522

American (AMR) AF: 0.0514 AC: 786 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.0630 AC: 304 AN: 4822

European-Finnish (FIN) AF: 0.0921 AC: 975 AN: 10592

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8332 AN: 67988

Other (OTH) AF: 0.0558 AC: 118 AN: 2114

Alfa AF: 0.102 Hom.: 1583

Bravo AF: 0.0703

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.69
PhyloP100		-0.0030
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs11568663; hg19: chr13-95822761;