NM_005688.4:c.3854+1820T>C

Variant names:

• chr3-183936081-A-G
• rs2139560
• NM_005688.4:c.3854+1820T>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.3854+1820T>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 151,808 control chromosomes in the GnomAD database, including 31,027 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 (31027 hom., cov: 30)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28
• Publications: 12 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 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.3854+1820T>C		intron	N/A	NP_005679.2
	ABCC5	NM_001320032.2		c.2438+1820T>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.3854+1820T>C		intron	N/A	ENSP00000333926.6
	ABCC5	ENST00000265586.10	TSL:5	c.3725+1820T>C		intron	N/A	ENSP00000265586.6
	ABCC5	ENST00000437205.5	TSL:5	n.*2547+1820T>C		intron	N/A	ENSP00000403510.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95468 AN: 151690 Hom.: 30974 Cov.: 30

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.611

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: 95577 AN: 151808 Hom.: 31027 Cov.: 30 AF XY: 0.624 AC XY: 46258 AN XY: 74164

African (AFR) AF: 0.784 AC: 32442 AN: 41396

American (AMR) AF: 0.591 AC: 9017 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1963 AN: 3470

East Asian (EAS) AF: 0.840 AC: 4326 AN: 5148

South Asian (SAS) AF: 0.566 AC: 2708 AN: 4788

European-Finnish (FIN) AF: 0.501 AC: 5279 AN: 10532

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

European-Non Finnish (NFE) AF: 0.558 AC: 37874 AN: 67918

Other (OTH) AF: 0.641 AC: 1349 AN: 2106

Alfa AF: 0.338 Hom.: 3531

Bravo AF: 0.643

Asia WGS AF: 0.728 AC: 2533 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	1.2
DANN	Benign	0.27
PhyloP100		-3.3
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: rs2139560; hg19: chr3-183653869;