chr13-95236417-T-C

Variant names:

• chr13-95236417-T-C
• rs9634642
• NM_005845.5:c.307-1583A>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.307-1583A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,990 control chromosomes in the GnomAD database, including 19,146 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 0.49 (19146 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.654
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.307-1583A>G		intron_variant	Intron 3 of 30	ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.307-1583A>G		intron_variant	Intron 3 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74061 AN: 151870 Hom.: 19143 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.487 AC: 74077 AN: 151990 Hom.: 19146 Cov.: 32 AF XY: 0.489 AC XY: 36364 AN XY: 74290

African (AFR) AF: 0.307 AC: 12753 AN: 41480

American (AMR) AF: 0.546 AC: 8346 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1962 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2939 AN: 5164

South Asian (SAS) AF: 0.516 AC: 2486 AN: 4818

European-Finnish (FIN) AF: 0.558 AC: 5893 AN: 10554

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37754 AN: 67912

Other (OTH) AF: 0.515 AC: 1088 AN: 2112

Alfa AF: 0.541 Hom.: 38248

Bravo AF: 0.480

Asia WGS AF: 0.526 AC: 1834 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	11
DANN	Benign	0.75
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9634642; hg19: chr13-95888671;