13-95083350-G-T

Variant names:

• chr13-95083350-G-T
• rs1189437
• NM_005845.5:c.2536-60C>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.2536-60C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 1,587,350 control chromosomes in the GnomAD database, including 707,066 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 0.91 (62991 hom., cov: 29)
  • Exomes 𝑓: 0.95 (644075 hom.)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 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.2536-60C>A		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.2395-60C>A		intron	N/A	NP_001288758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.2536-60C>A		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000646439.1		c.2395-60C>A		intron	N/A	ENSP00000494751.1
	ABCC4	ENST00000643051.1		n.*161-60C>A		intron	N/A	ENSP00000495513.1

Frequencies

GnomAD3 genomes AF: 0.908 AC: 138025 AN: 152026 Hom.: 62949 Cov.: 29

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.930

GnomAD4 exome AF: 0.946 AC: 1358262 AN: 1435206 Hom.: 644075 AF XY: 0.947 AC XY: 675285 AN XY: 713072

African (AFR) AF: 0.823 AC: 26432 AN: 32132

American (AMR) AF: 0.926 AC: 37896 AN: 40912

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 24110 AN: 25214

East Asian (EAS) AF: 0.749 AC: 29264 AN: 39056

South Asian (SAS) AF: 0.955 AC: 80012 AN: 83740

European-Finnish (FIN) AF: 0.915 AC: 48280 AN: 52778

Middle Eastern (MID) AF: 0.946 AC: 5307 AN: 5608

European-Non Finnish (NFE) AF: 0.959 AC: 1051487 AN: 1096518

Other (OTH) AF: 0.936 AC: 55474 AN: 59248

GnomAD4 genome AF: 0.908 AC: 138123 AN: 152144 Hom.: 62991 Cov.: 29 AF XY: 0.907 AC XY: 67464 AN XY: 74386

African (AFR) AF: 0.828 AC: 34336 AN: 41486

American (AMR) AF: 0.926 AC: 14137 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 3333 AN: 3472

East Asian (EAS) AF: 0.778 AC: 4025 AN: 5172

South Asian (SAS) AF: 0.946 AC: 4537 AN: 4796

European-Finnish (FIN) AF: 0.916 AC: 9717 AN: 10604

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 64946 AN: 68020

Other (OTH) AF: 0.929 AC: 1963 AN: 2114

Alfa AF: 0.944 Hom.: 108624

Bravo AF: 0.905

Asia WGS AF: 0.862 AC: 3000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.26
PhyloP100		0.62
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: rs1189437; hg19: chr13-95735604;