13-95185468-A-G

Variant names:

• chr13-95185468-A-G
• rs1564351
• NM_005845.5:c.1545+1233T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005845.5(ABCC4):​c.1545+1233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 152,286 control chromosomes in the GnomAD database, including 655 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 0.091 (655 hom., cov: 33)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 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.1545+1233T>C		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.1545+1233T>C		intron	N/A	NP_001288758.1
	ABCC4	NM_001105515.3		c.1545+1233T>C		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.1545+1233T>C		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.1545+1233T>C		intron	N/A	ENSP00000487081.1
	ABCC4	ENST00000646439.1		c.1545+1233T>C		intron	N/A	ENSP00000494751.1

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13866 AN: 152168 Hom.: 651 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0741

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.0760

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.0937

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

GnomAD4 genome AF: 0.0912 AC: 13887 AN: 152286 Hom.: 655 Cov.: 33 AF XY: 0.0899 AC XY: 6696 AN XY: 74456

African (AFR) AF: 0.106 AC: 4424 AN: 41558

American (AMR) AF: 0.0740 AC: 1132 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 182 AN: 3470

East Asian (EAS) AF: 0.106 AC: 547 AN: 5180

South Asian (SAS) AF: 0.0383 AC: 185 AN: 4824

European-Finnish (FIN) AF: 0.0760 AC: 807 AN: 10616

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0936 AC: 6363 AN: 68016

Other (OTH) AF: 0.0932 AC: 197 AN: 2114

Alfa AF: 0.0902 Hom.: 738

Bravo AF: 0.0915

Asia WGS AF: 0.0620 AC: 215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		1.8
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: rs1564351; hg19: chr13-95837722;