13-95251181-T-C

Variant names:

• chr13-95251181-T-C
• rs4148434
• NM_005845.5:c.75-3428A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005845.5(ABCC4):​c.75-3428A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 151,930 control chromosomes in the GnomAD database, including 31,855 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 0.65 (31855 hom., cov: 31)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.75-3428A>G		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.75-3428A>G		intron_variant	Intron 1 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98196 AN: 151812 Hom.: 31841 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.647 AC: 98252 AN: 151930 Hom.: 31855 Cov.: 31 AF XY: 0.648 AC XY: 48119 AN XY: 74256

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.650

Alfa AF: 0.642 Hom.: 41188

Bravo AF: 0.647

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.79

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: rs4148434; hg19: chr13-95903435;