rs7476245

Positions:

• chr10-99834972-G-A

Variant summary

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

The NM_000392.5(ABCC2):​c.3414+437G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,254 control chromosomes in the GnomAD database, including 827 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 0.088 (827 hom., cov: 32)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997

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).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC2	NM_000392.5	c.3414+437G>A		intron_variant		ENST00000647814.1	NP_000383.2
ABCC2	XM_006717630.4	c.2718+437G>A		intron_variant			XP_006717693.1
ABCC2	XM_047424598.1	c.3414+437G>A		intron_variant			XP_047280554.1
ABCC2	XR_945604.4	n.3619+437G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1	c.3414+437G>A		intron_variant			NM_000392.5	ENSP00000497274	P1

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13381 AN: 152136 Hom.: 830 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.0580

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0573

Gnomad OTH AF: 0.0861

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

GnomAD4 genome AF: 0.0879 AC: 13387 AN: 152254 Hom.: 827 Cov.: 32 AF XY: 0.0864 AC XY: 6435 AN XY: 74444

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.0740

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.0579

Gnomad4 FIN AF: 0.0379

Gnomad4 NFE AF: 0.0572

Gnomad4 OTH AF: 0.0852

Alfa AF: 0.0672 Hom.: 409

Bravo AF: 0.0961

Asia WGS AF: 0.0370 AC: 130 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	0.14
DANN	Benign	0.57

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: rs7476245; hg19: chr10-101594729;