rs1189470

Variant names:

• chr13-95149478-C-A
• rs1189470
• NM_005845.5:c.2455+11711G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-95149478-C-A
• chr13-95149478-C-G
• chr13-95149478-C-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+11711G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,194 control chromosomes in the GnomAD database, including 60,073 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 0.89 (60073 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 4 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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.2455+11711G>T		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.2314+11711G>T		intron	N/A	NP_001288758.1
	ABCC4	NM_001105515.3		c.2455+11711G>T		intron	N/A	NP_001098985.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.2455+11711G>T		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.2455+11711G>T		intron	N/A	ENSP00000487081.1
	ABCC4	ENST00000646439.1		c.2314+11711G>T		intron	N/A	ENSP00000494751.1

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134655 AN: 152076 Hom.: 60001 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.886 AC: 134786 AN: 152194 Hom.: 60073 Cov.: 32 AF XY: 0.892 AC XY: 66361 AN XY: 74394

African (AFR) AF: 0.967 AC: 40166 AN: 41546

American (AMR) AF: 0.896 AC: 13689 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2925 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5176 AN: 5182

South Asian (SAS) AF: 0.967 AC: 4660 AN: 4818

European-Finnish (FIN) AF: 0.888 AC: 9395 AN: 10580

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55921 AN: 67996

Other (OTH) AF: 0.878 AC: 1856 AN: 2114

Alfa AF: 0.869 Hom.: 16089

Bravo AF: 0.888

Asia WGS AF: 0.977 AC: 3396 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		0.49
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: rs1189470; hg19: chr13-95801732;