rs11597282

Positions:

• chr10-99830263-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000392.5(ABCC2):​c.2621-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,613,100 control chromosomes in the GnomAD database, including 943 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 0.024 (55 hom., cov: 32)
  • Exomes 𝑓: 0.032 (888 hom.)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445

Genes affected

ABCC2 (HGNC:53): (ATP binding cassette subfamily C member 2) 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 protein is expressed in the canalicular (apical) part of the hepatocyte and functions in biliary transport. Substrates include anticancer drugs such as vinblastine; therefore, this protein appears to contribute to drug resistance in mammalian cells. Several different mutations in this gene have been observed in patients with Dubin-Johnson syndrome (DJS), an autosomal recessive disorder characterized by conjugated hyperbilirubinemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0242 (3678/152108) while in subpopulation NFE AF= 0.0354 (2408/67994). AF 95% confidence interval is 0.0342. There are 55 homozygotes in gnomad4. There are 1781 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 55 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC2	NM_000392.5	c.2621-44G>A		intron_variant		ENST00000647814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC2	ENST00000647814.1	c.2621-44G>A		intron_variant			NM_000392.5	P1

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3683 AN: 151990 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.00580

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0290

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0312

GnomAD3 exomes AF: 0.0255 AC: 6413 AN: 251284 Hom.: 98 AF XY: 0.0258 AC XY: 3501 AN XY: 135798

Gnomad AFR exome AF: 0.00560

Gnomad AMR exome AF: 0.0267

Gnomad ASJ exome AF: 0.0294

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0151

Gnomad FIN exome AF: 0.0139

Gnomad NFE exome AF: 0.0366

Gnomad OTH exome AF: 0.0284

GnomAD4 exome AF: 0.0315 AC: 46042 AN: 1460992 Hom.: 888 Cov.: 32 AF XY: 0.0312 AC XY: 22660 AN XY: 726872

Gnomad4 AFR exome AF: 0.00454

Gnomad4 AMR exome AF: 0.0280

Gnomad4 ASJ exome AF: 0.0322

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0153

Gnomad4 FIN exome AF: 0.0140

Gnomad4 NFE exome AF: 0.0359

Gnomad4 OTH exome AF: 0.0273

GnomAD4 genome AF: 0.0242 AC: 3678 AN: 152108 Hom.: 55 Cov.: 32 AF XY: 0.0240 AC XY: 1781 AN XY: 74358

Gnomad4 AFR AF: 0.00579

Gnomad4 AMR AF: 0.0353

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0162

Gnomad4 FIN AF: 0.0132

Gnomad4 NFE AF: 0.0354

Gnomad4 OTH AF: 0.0304

Alfa AF: 0.0308 Hom.: 48

Bravo AF: 0.0251

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs11597282; hg19: chr10-101590020; COSMIC: COSV64984366;