rs1401999

Variant names:

• chr3-183960554-C-G
• rs1401999
• NM_005688.4:c.2380-719G>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.2380-719G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,050 control chromosomes in the GnomAD database, including 31,128 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 0.63 (31128 hom., cov: 31)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 34 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005688.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC5	NM_005688.4	MANE Select	c.2380-719G>C		intron	N/A	NP_005679.2
	ABCC5	NM_001320032.2		c.964-719G>C		intron	N/A	NP_001306961.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC5	ENST00000334444.11	TSL:1 MANE Select	c.2380-719G>C		intron	N/A	ENSP00000333926.6
	ABCC5	ENST00000265586.10	TSL:5	c.2380-719G>C		intron	N/A	ENSP00000265586.6
	ABCC5	ENST00000437205.5	TSL:5	n.*1073-719G>C		intron	N/A	ENSP00000403510.1

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95647 AN: 151932 Hom.: 31076 Cov.: 31

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.630 AC: 95754 AN: 152050 Hom.: 31128 Cov.: 31 AF XY: 0.624 AC XY: 46357 AN XY: 74316

African (AFR) AF: 0.785 AC: 32560 AN: 41490

American (AMR) AF: 0.586 AC: 8952 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1917 AN: 3472

East Asian (EAS) AF: 0.861 AC: 4450 AN: 5166

South Asian (SAS) AF: 0.561 AC: 2702 AN: 4814

European-Finnish (FIN) AF: 0.501 AC: 5293 AN: 10558

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37935 AN: 67970

Other (OTH) AF: 0.641 AC: 1354 AN: 2112

Alfa AF: 0.584 Hom.: 3311

Bravo AF: 0.643

Asia WGS AF: 0.732 AC: 2546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.24
PhyloP100		-0.25
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: rs1401999; hg19: chr3-183678342;