rs7324283

Variant names:

• chr13-95281416-C-A
• rs7324283
• NM_005845.5:c.74+19825G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-95281416-C-A
• chr13-95281416-C-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.74+19825G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,466 control chromosomes in the GnomAD database, including 30,921 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 0.63 (30921 hom., cov: 29)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448
• 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

LOC124903192 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.74+19825G>T		intron_variant	Intron 1 of 30	ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.74+19825G>T		intron_variant	Intron 1 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 94993 AN: 151348 Hom.: 30908 Cov.: 29

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.628 AC: 95045 AN: 151466 Hom.: 30921 Cov.: 29 AF XY: 0.630 AC XY: 46614 AN XY: 73972

African (AFR) AF: 0.443 AC: 18277 AN: 41232

American (AMR) AF: 0.712 AC: 10795 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2514 AN: 3470

East Asian (EAS) AF: 0.581 AC: 2987 AN: 5140

South Asian (SAS) AF: 0.656 AC: 3144 AN: 4792

European-Finnish (FIN) AF: 0.754 AC: 7860 AN: 10418

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47358 AN: 67954

Other (OTH) AF: 0.661 AC: 1389 AN: 2100

Alfa AF: 0.676 Hom.: 40668

Bravo AF: 0.619

Asia WGS AF: 0.609 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.73
PhyloP100		-0.45
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: rs7324283; hg19: chr13-95933670;