13-95021686-G-GA

Variant names:

• chr13-95021686-G-GA
• rs4148550
• NM_005845.5:c.3871-5dupT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_005845.5(ABCC4):​c.3871-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,223,308 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000074 (0 hom., cov: 33)
  • Exomes 𝑓: 0.012 (0 hom.)
• Consequence: ABCC4 NM_005845.5 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0710

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 13-95021686-G-GA is Benign according to our data. Variant chr13-95021686-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 3059729.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.3871-5dupT		splice_region_variant, intron_variant	Intron 30 of 30	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.3730-5dupT		splice_region_variant, intron_variant	Intron 29 of 29		NP_001288758.1
ABCC4	XM_047430034.1	c.3742-5dupT		splice_region_variant, intron_variant	Intron 30 of 30		XP_047285990.1
ABCC4	XM_047430035.1	c.3322-5dupT		splice_region_variant, intron_variant	Intron 27 of 27		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.3871-5_3871-4insT		splice_region_variant, intron_variant	Intron 30 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.0000740 AC: 11 AN: 148708 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000671

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000589

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000893

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0122 AC: 13069 AN: 1074514 Hom.: 0 Cov.: 25 AF XY: 0.0115 AC XY: 6163 AN XY: 536510

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.0103

Gnomad4 EAS exome AF: 0.00668

Gnomad4 SAS exome AF: 0.0110

Gnomad4 FIN exome AF: 0.00415

Gnomad4 NFE exome AF: 0.0129

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.0000739 AC: 11 AN: 148794 Hom.: 0 Cov.: 33 AF XY: 0.0000967 AC XY: 7 AN XY: 72392

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000670

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000591

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000102

Gnomad4 NFE AF: 0.0000894

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0293 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ABCC4-related disorder Benign:1

Feb 12, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs4148550; hg19: chr13-95673940;