chr13-95056818-T-C

Variant names:

• chr13-95056818-T-C
• rs1750190
• NM_005845.5:c.3367-3634A>G

Variant summary

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

The ENST00000645237.2(ABCC4):​c.3367-3634A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,034 control chromosomes in the GnomAD database, including 20,607 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 0.51 (20607 hom., cov: 33)
• Consequence: ABCC4 ENST00000645237.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 5 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 = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645237.2. 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.3367-3634A>G		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.3226-3634A>G		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.3367-3634A>G		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000646439.1		c.3226-3634A>G		intron	N/A	ENSP00000494751.1
	ABCC4	ENST00000643051.1		n.*992-963A>G		intron	N/A	ENSP00000495513.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78167 AN: 151916 Hom.: 20582 Cov.: 33

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.515 AC: 78239 AN: 152034 Hom.: 20607 Cov.: 33 AF XY: 0.505 AC XY: 37512 AN XY: 74306

African (AFR) AF: 0.581 AC: 24082 AN: 41484

American (AMR) AF: 0.454 AC: 6935 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1910 AN: 3466

East Asian (EAS) AF: 0.329 AC: 1702 AN: 5166

South Asian (SAS) AF: 0.332 AC: 1599 AN: 4812

European-Finnish (FIN) AF: 0.417 AC: 4400 AN: 10552

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35970 AN: 67960

Other (OTH) AF: 0.489 AC: 1029 AN: 2104

Alfa AF: 0.520 Hom.: 32570

Bravo AF: 0.524

Asia WGS AF: 0.342 AC: 1190 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.39
DANN	Benign	0.40
PhyloP100		-0.53
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: rs1750190; hg19: chr13-95709072;