rs1402003

Variant names:

• chr3-183925091-G-A
• rs1402003
• NM_005688.4:c.4212+464C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-183925091-G-A
• chr3-183925091-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005688.4(ABCC5):​c.4212+464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,112 control chromosomes in the GnomAD database, including 30,107 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 0.62 (30107 hom., cov: 33)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 11 publications found

Genes affected

ABCC5 (HGNC:56): (ATP binding cassette subfamily C member 5) 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 functions in the cellular export of its substrate, cyclic nucleotides. This export contributes to the degradation of phosphodiesterases and possibly an elimination pathway for cyclic nucleotides. Studies show that this protein provides resistance to thiopurine anticancer drugs, 6-mercatopurine and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine. This protein may be involved in resistance to thiopurines in acute lymphoblastic leukemia and antiretroviral nucleoside analogs in HIV-infected patients. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC5	NM_005688.4	c.4212+464C>T		intron_variant	Intron 29 of 29	ENST00000334444.11	NP_005679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444.11	c.4212+464C>T		intron_variant	Intron 29 of 29	1	NM_005688.4	ENSP00000333926.6
ABCC5	ENST00000265586.10	c.4083+464C>T		intron_variant	Intron 28 of 28	5		ENSP00000265586.6
ABCC5	ENST00000437205.5	n.*2905+464C>T		intron_variant	Intron 29 of 29	5		ENSP00000403510.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94346 AN: 151994 Hom.: 30062 Cov.: 33

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.621 AC: 94447 AN: 152112 Hom.: 30107 Cov.: 33 AF XY: 0.615 AC XY: 45735 AN XY: 74358

African (AFR) AF: 0.754 AC: 31308 AN: 41496

American (AMR) AF: 0.587 AC: 8975 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1959 AN: 3472

East Asian (EAS) AF: 0.841 AC: 4367 AN: 5192

South Asian (SAS) AF: 0.564 AC: 2716 AN: 4818

European-Finnish (FIN) AF: 0.501 AC: 5298 AN: 10578

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37866 AN: 67954

Other (OTH) AF: 0.633 AC: 1337 AN: 2112

Alfa AF: 0.572 Hom.: 6883

Bravo AF: 0.632

Asia WGS AF: 0.726 AC: 2524 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	0.042
DANN	Benign	0.49
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1402003; hg19: chr3-183642879;