rs7993878

Variant names:

• chr13-95041453-G-A
• rs7993878
• NM_005845.5:c.3735+2229C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005845.5(ABCC4):​c.3735+2229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,114 control chromosomes in the GnomAD database, including 2,968 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 0.18 (2968 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.640
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 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.3735+2229C>T		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.3594+2229C>T		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.3735+2229C>T		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000646439.1		c.3594+2229C>T		intron	N/A	ENSP00000494751.1
	ABCC4	ENST00000471041.2	TSL:4	n.605+2229C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26925 AN: 151996 Hom.: 2961 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0374

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.177 AC: 26949 AN: 152114 Hom.: 2968 Cov.: 32 AF XY: 0.174 AC XY: 12963 AN XY: 74356

African (AFR) AF: 0.307 AC: 12750 AN: 41490

American (AMR) AF: 0.112 AC: 1705 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3470

East Asian (EAS) AF: 0.0373 AC: 193 AN: 5176

South Asian (SAS) AF: 0.100 AC: 484 AN: 4820

European-Finnish (FIN) AF: 0.156 AC: 1646 AN: 10570

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9096 AN: 67986

Other (OTH) AF: 0.161 AC: 340 AN: 2114

Alfa AF: 0.140 Hom.: 2897

Bravo AF: 0.180

Asia WGS AF: 0.0810 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.67
PhyloP100		0.64
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: rs7993878; hg19: chr13-95693707;