chr13-95245953-A-G

Variant names:

• chr13-95245953-A-G
• rs4148441
• NM_005845.5:c.306+1022T>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.306+1022T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 149,294 control chromosomes in the GnomAD database, including 60,984 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 0.90 (60984 hom., cov: 21)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.800
• Publications: 19 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 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.306+1022T>C		intron	N/A	NP_005836.2	O15439-1
	ABCC4	NM_001301829.2		c.306+1022T>C		intron	N/A	NP_001288758.1	O15439-2
	ABCC4	NM_001105515.3		c.306+1022T>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.306+1022T>C		intron	N/A	ENSP00000494609.1	O15439-1
	ABCC4	ENST00000629385.1	TSL:1	c.306+1022T>C		intron	N/A	ENSP00000487081.1	O15439-3
	ABCC4	ENST00000967420.1		c.306+1022T>C		intron	N/A	ENSP00000637479.1

Frequencies

GnomAD3 genomes AF: 0.903 AC: 134696 AN: 149168 Hom.: 60933 Cov.: 21

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.808

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.886

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

GnomAD4 genome AF: 0.903 AC: 134809 AN: 149294 Hom.: 60984 Cov.: 21 AF XY: 0.901 AC XY: 65453 AN XY: 72622

African (AFR) AF: 0.937 AC: 37906 AN: 40448

American (AMR) AF: 0.857 AC: 12838 AN: 14974

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2716 AN: 3456

East Asian (EAS) AF: 0.783 AC: 3837 AN: 4902

South Asian (SAS) AF: 0.821 AC: 3822 AN: 4654

European-Finnish (FIN) AF: 0.932 AC: 9369 AN: 10056

Middle Eastern (MID) AF: 0.810 AC: 235 AN: 290

European-Non Finnish (NFE) AF: 0.911 AC: 61572 AN: 67558

Other (OTH) AF: 0.886 AC: 1823 AN: 2058

Alfa AF: 0.901 Hom.: 282492

Bravo AF: 0.899

Asia WGS AF: 0.800 AC: 2779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.1
DANN	Benign	0.64
PhyloP100		0.80
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: rs4148441; hg19: chr13-95898207;