rs4148512

Variant names:

• chr13-95139474-G-A
• rs4148512
• NM_005845.5:c.2455+21715C>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.2455+21715C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,078 control chromosomes in the GnomAD database, including 5,996 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 0.27 (5996 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 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.2455+21715C>T		intron	N/A	NP_005836.2	O15439-1
	ABCC4	NM_001301829.2		c.2314+21715C>T		intron	N/A	NP_001288758.1	O15439-2
	ABCC4	NM_001105515.3		c.2455+21715C>T		intron	N/A	NP_001098985.1	O15439-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.2455+21715C>T		intron	N/A	ENSP00000494609.1	O15439-1
	ABCC4	ENST00000629385.1	TSL:1	c.2455+21715C>T		intron	N/A	ENSP00000487081.1	O15439-3
	ABCC4	ENST00000967420.1		c.2455+21715C>T		intron	N/A	ENSP00000637479.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40915 AN: 151962 Hom.: 5988 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.269 AC: 40944 AN: 152078 Hom.: 5996 Cov.: 32 AF XY: 0.268 AC XY: 19902 AN XY: 74336

African (AFR) AF: 0.386 AC: 15994 AN: 41478

American (AMR) AF: 0.286 AC: 4375 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3468

East Asian (EAS) AF: 0.151 AC: 782 AN: 5168

South Asian (SAS) AF: 0.251 AC: 1212 AN: 4820

European-Finnish (FIN) AF: 0.218 AC: 2311 AN: 10580

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14563 AN: 67962

Other (OTH) AF: 0.281 AC: 594 AN: 2112

Alfa AF: 0.236 Hom.: 14115

Bravo AF: 0.281

Asia WGS AF: 0.211 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.27
PhyloP100		-1.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4148512;

hg19: chr13-95791728;