13-95228229-A-G

Variant names:

• chr13-95228229-A-G
• rs4773856
• NM_005845.5:c.531+6381T>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.531+6381T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,050 control chromosomes in the GnomAD database, including 41,835 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 0.74 (41835 hom., cov: 31)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 3 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.845 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.531+6381T>C		intron	N/A	NP_005836.2	O15439-1
	ABCC4	NM_001301829.2		c.531+6381T>C		intron	N/A	NP_001288758.1	O15439-2
	ABCC4	NM_001105515.3		c.531+6381T>C		intron	N/A	NP_001098985.1	O15439-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.531+6381T>C		intron	N/A	ENSP00000494609.1	O15439-1
	ABCC4	ENST00000629385.1	TSL:1	c.531+6381T>C		intron	N/A	ENSP00000487081.1	O15439-3
	ABCC4	ENST00000967420.1		c.531+6381T>C		intron	N/A	ENSP00000637479.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112527 AN: 151932 Hom.: 41793 Cov.: 31

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.741 AC: 112623 AN: 152050 Hom.: 41835 Cov.: 31 AF XY: 0.742 AC XY: 55157 AN XY: 74320

African (AFR) AF: 0.742 AC: 30746 AN: 41462

American (AMR) AF: 0.751 AC: 11490 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2613 AN: 3470

East Asian (EAS) AF: 0.763 AC: 3936 AN: 5156

South Asian (SAS) AF: 0.867 AC: 4161 AN: 4798

European-Finnish (FIN) AF: 0.704 AC: 7443 AN: 10576

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49762 AN: 67978

Other (OTH) AF: 0.738 AC: 1560 AN: 2114

Alfa AF: 0.734 Hom.: 33342

Bravo AF: 0.740

Asia WGS AF: 0.800 AC: 2781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.45
PhyloP100		-0.34
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: rs4773856; hg19: chr13-95880483;