13-95021537-A-C

Position:

• chr13-95021537-A-C

Variant summary

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

The NM_005845.5(ABCC4):​c.*38T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,474,528 control chromosomes in the GnomAD database, including 121,508 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 0.38 (11040 hom., cov: 32)
  • Exomes 𝑓: 0.41 (110468 hom.)
• Consequence: ABCC4 NM_005845.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.*38T>G		3_prime_UTR_variant	31/31	ENST00000645237.2
ABCC4	NM_001301829.2	c.*38T>G		3_prime_UTR_variant	30/30
ABCC4	XM_047430034.1	c.*38T>G		3_prime_UTR_variant	31/31
ABCC4	XM_047430035.1	c.*38T>G		3_prime_UTR_variant	28/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.*38T>G		3_prime_UTR_variant	31/31		NM_005845.5	P1
ABCC4	ENST00000643051.1	c.*1927T>G		3_prime_UTR_variant, NMD_transcript_variant	33/33
ABCC4	ENST00000643842.1	c.*4062T>G		3_prime_UTR_variant, NMD_transcript_variant	32/32
ABCC4	ENST00000646439.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57546 AN: 151954 Hom.: 11040 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.396

GnomAD3 exomes AF: 0.410 AC: 99007 AN: 241270 Hom.: 20725 AF XY: 0.413 AC XY: 53802 AN XY: 130204

Gnomad AFR exome AF: 0.322

Gnomad AMR exome AF: 0.467

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.512

Gnomad SAS exome AF: 0.494

Gnomad FIN exome AF: 0.329

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.406 AC: 536675 AN: 1322456 Hom.: 110468 Cov.: 20 AF XY: 0.408 AC XY: 271112 AN XY: 664278

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.459

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.498

Gnomad4 SAS exome AF: 0.489

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.404

GnomAD4 genome AF: 0.379 AC: 57567 AN: 152072 Hom.: 11040 Cov.: 32 AF XY: 0.377 AC XY: 28044 AN XY: 74308

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.400

Alfa AF: 0.392 Hom.: 19782

Bravo AF: 0.385

Asia WGS AF: 0.484 AC: 1682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3742106; hg19: chr13-95673791; COSMIC: COSV65316236; COSMIC: COSV65316236;