13-95020696-A-G

Variant names:

• chr13-95020696-A-G
• rs1059751
• NM_005845.5:c.*879T>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.*879T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,108 control chromosomes in the GnomAD database, including 13,866 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 0.42 (13862 hom., cov: 32)
  • Exomes 𝑓: 0.65 (4 hom.)
• Consequence: ABCC4 NM_005845.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 28 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 (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.*879T>C		3_prime_UTR_variant	Exon 31 of 31	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.*879T>C		3_prime_UTR_variant	Exon 30 of 30		NP_001288758.1
ABCC4	XM_047430034.1	c.*879T>C		3_prime_UTR_variant	Exon 31 of 31		XP_047285990.1
ABCC4	XM_047430035.1	c.*879T>C		3_prime_UTR_variant	Exon 28 of 28		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.*879T>C		3_prime_UTR_variant	Exon 31 of 31		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63299 AN: 151970 Hom.: 13861 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.650 AC: 13 AN: 20 Hom.: 4 Cov.: 0 AF XY: 0.571 AC XY: 8 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.650 AC: 13 AN: 20

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.416 AC: 63302 AN: 152088 Hom.: 13862 Cov.: 32 AF XY: 0.423 AC XY: 31453 AN XY: 74324

African (AFR) AF: 0.288 AC: 11959 AN: 41478

American (AMR) AF: 0.369 AC: 5634 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1513 AN: 3472

East Asian (EAS) AF: 0.494 AC: 2556 AN: 5176

South Asian (SAS) AF: 0.479 AC: 2315 AN: 4828

European-Finnish (FIN) AF: 0.603 AC: 6377 AN: 10568

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31533 AN: 67972

Other (OTH) AF: 0.405 AC: 853 AN: 2108

Alfa AF: 0.437 Hom.: 43957

Bravo AF: 0.390

Asia WGS AF: 0.454 AC: 1579 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	3.7
DANN	Benign	0.60
PhyloP100		0.28
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: rs1059751; hg19: chr13-95672950;