13-95177427-T-C

Variant names:

• chr13-95177427-T-C
• rs1678405
• NM_005845.5:c.1727+280A>G

Variant summary

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

The NM_005845.5(ABCC4):​c.1727+280A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,978 control chromosomes in the GnomAD database, including 14,900 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 (14900 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.1727+280A>G		intron_variant	Intron 13 of 30	ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.1727+280A>G		intron_variant	Intron 13 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63269 AN: 151860 Hom.: 14874 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.417 AC: 63333 AN: 151978 Hom.: 14900 Cov.: 32 AF XY: 0.411 AC XY: 30560 AN XY: 74274

African (AFR) AF: 0.655 AC: 27128 AN: 41440

American (AMR) AF: 0.395 AC: 6039 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1461 AN: 3464

East Asian (EAS) AF: 0.410 AC: 2108 AN: 5138

South Asian (SAS) AF: 0.263 AC: 1268 AN: 4814

European-Finnish (FIN) AF: 0.277 AC: 2929 AN: 10558

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21110 AN: 67980

Other (OTH) AF: 0.410 AC: 864 AN: 2108

Alfa AF: 0.345 Hom.: 12063

Bravo AF: 0.441

Asia WGS AF: 0.380 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.43
PhyloP100		-0.40
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: rs1678405; hg19: chr13-95829681;