13-95273060-G-T

Variant names:

• chr13-95273060-G-T
• rs17268282
• NM_005845.5:c.75-25307C>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.75-25307C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0544 in 152,144 control chromosomes in the GnomAD database, including 271 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 0.054 (271 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.75-25307C>A		intron_variant	Intron 1 of 30	ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.75-25307C>A		intron_variant	Intron 1 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.0543 AC: 8260 AN: 152026 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0631

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

GnomAD4 genome AF: 0.0544 AC: 8270 AN: 152144 Hom.: 271 Cov.: 32 AF XY: 0.0540 AC XY: 4014 AN XY: 74368

African (AFR) AF: 0.0415 AC: 1722 AN: 41496

American (AMR) AF: 0.0489 AC: 747 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4818

European-Finnish (FIN) AF: 0.0694 AC: 734 AN: 10578

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0674 AC: 4586 AN: 68002

Other (OTH) AF: 0.0620 AC: 131 AN: 2114

Alfa AF: 0.0604 Hom.: 482

Bravo AF: 0.0514

Asia WGS AF: 0.0290 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	14
DANN	Benign	0.63
PhyloP100		0.36
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: rs17268282; hg19: chr13-95925314;