NM_005845.5:c.2686+2016T>C

Variant names:

• chr13-95081124-A-G
• rs1751052
• NM_005845.5:c.2686+2016T>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.2686+2016T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 151,838 control chromosomes in the GnomAD database, including 52,586 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 0.82 (52586 hom., cov: 31)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.916 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.2686+2016T>C		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.2545+2016T>C		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.2686+2016T>C		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000967420.1		c.2686+2016T>C		intron	N/A	ENSP00000637479.1
	ABCC4	ENST00000967421.1		c.2683+2016T>C		intron	N/A	ENSP00000637480.1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124441 AN: 151720 Hom.: 52570 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.855

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

GnomAD4 genome AF: 0.820 AC: 124498 AN: 151838 Hom.: 52586 Cov.: 31 AF XY: 0.821 AC XY: 60928 AN XY: 74218

African (AFR) AF: 0.598 AC: 24779 AN: 41440

American (AMR) AF: 0.874 AC: 13325 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3068 AN: 3466

East Asian (EAS) AF: 0.788 AC: 4064 AN: 5160

South Asian (SAS) AF: 0.918 AC: 4428 AN: 4824

European-Finnish (FIN) AF: 0.889 AC: 9394 AN: 10562

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62548 AN: 67838

Other (OTH) AF: 0.856 AC: 1802 AN: 2104

Alfa AF: 0.913 Hom.: 272431

Bravo AF: 0.825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.58
PhyloP100		-0.090
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: rs1751052; hg19: chr13-95733378;