rs1189457

chr13-95067240-G-Cchr13-95067240-G-T

Variant summary

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

The NM_005845.5(ABCC4):c.3211-4381C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,984 control chromosomes in the GnomAD database, including 25,958 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 0.58 (25958 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.3211-4381C>G		intron_variant		ENST00000645237.2
ABCC4	NM_001301829.2	c.3070-4381C>G		intron_variant
ABCC4	XM_047430034.1	c.3082-4381C>G		intron_variant
ABCC4	XM_047430035.1	c.2662-4381C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.3211-4381C>G		intron_variant			NM_005845.5	P1
ABCC4	ENST00000646439.1	c.3070-4381C>G		intron_variant
ABCC4	ENST00000643051.1	c.*836-4381C>G		intron_variant, NMD_transcript_variant
ABCC4	ENST00000643842.1	c.*3257-4381C>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88366 AN: 151866 Hom.: 25960 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.582 AC: 88400 AN: 151984 Hom.: 25958 Cov.: 32 AF XY: 0.589 AC XY: 43777 AN XY: 74286

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.613

Alfa AF: 0.590 Hom.: 3338

Bravo AF: 0.570

Asia WGS AF: 0.614 AC: 2138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.031
Dann	Benign	0.37

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: rs1189457; hg19: chr13-95719494;