rs4148550

Variant names:

• chr13-95021686-GAA-G
• rs4148550
• NM_005845.5:c.3871-6_3871-5delTT

Your query was ambiguous. Multiple possible variants found:

• chr13-95021686-GAA-G
• chr13-95021686-GAA-GA
• chr13-95021686-GAA-GAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005845.5(ABCC4):​c.3871-6_3871-5delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,149,812 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: ABCC4 NM_005845.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.3871-6_3871-5delTT		splice_region intron	N/A	NP_005836.2	O15439-1
	ABCC4	NM_001301829.2		c.3730-6_3730-5delTT		splice_region intron	N/A	NP_001288758.1	O15439-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.3871-6_3871-5delTT		splice_region intron	N/A	ENSP00000494609.1	O15439-1
	ABCC4	ENST00000967420.1		c.3895-6_3895-5delTT		splice_region intron	N/A	ENSP00000637479.1
	ABCC4	ENST00000967421.1		c.3868-6_3868-5delTT		splice_region intron	N/A	ENSP00000637480.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000129 AC: 2 AN: 155452 AF XY: 0.0000237

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000272

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000435 AC: 5 AN: 1149812 Hom.: 0 AF XY: 0.00000522 AC XY: 3 AN XY: 574656

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25206

American (AMR) AF: 0.00 AC: 0 AN: 32180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20492

East Asian (EAS) AF: 0.00 AC: 0 AN: 32734

South Asian (SAS) AF: 0.00 AC: 0 AN: 65710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4890

European-Non Finnish (NFE) AF: 0.00000457 AC: 4 AN: 875646

Other (OTH) AF: 0.0000209 AC: 1 AN: 47874

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs4148550; hg19: chr13-95673940;