chr13-95247353-A-G

Variant names:

• chr13-95247353-A-G
• rs4148436
• NM_005845.5:c.186-258T>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.186-258T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,008 control chromosomes in the GnomAD database, including 10,897 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 0.38 (10897 hom., cov: 31)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• Publications: 14 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 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.186-258T>C		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.186-258T>C		intron	N/A	NP_001288758.1
	ABCC4	NM_001105515.3		c.186-258T>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.186-258T>C		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.186-258T>C		intron	N/A	ENSP00000487081.1
	ABCC4	ENST00000646439.1		c.186-258T>C		intron	N/A	ENSP00000494751.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57080 AN: 151890 Hom.: 10891 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.376 AC: 57105 AN: 152008 Hom.: 10897 Cov.: 31 AF XY: 0.376 AC XY: 27972 AN XY: 74300

African (AFR) AF: 0.382 AC: 15817 AN: 41444

American (AMR) AF: 0.376 AC: 5735 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1137 AN: 3472

East Asian (EAS) AF: 0.362 AC: 1872 AN: 5170

South Asian (SAS) AF: 0.290 AC: 1400 AN: 4826

European-Finnish (FIN) AF: 0.421 AC: 4440 AN: 10546

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25365 AN: 67968

Other (OTH) AF: 0.381 AC: 803 AN: 2110

Alfa AF: 0.374 Hom.: 17074

Bravo AF: 0.377

Asia WGS AF: 0.342 AC: 1189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.52
PhyloP100		0.39
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: rs4148436; hg19: chr13-95899607;