3-184015996-A-G

Variant names:

• chr3-184015996-A-G
• rs4148557
• NM_005688.4:c.-55-1549T>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.-55-1549T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,052 control chromosomes in the GnomAD database, including 27,416 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 0.60 (27416 hom., cov: 32)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 15 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC5	NM_005688.4	c.-55-1549T>C		intron_variant	Intron 1 of 29	ENST00000334444.11	NP_005679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444.11	c.-55-1549T>C		intron_variant	Intron 1 of 29	1	NM_005688.4	ENSP00000333926.6

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90506 AN: 151934 Hom.: 27394 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.596 AC: 90577 AN: 152052 Hom.: 27416 Cov.: 32 AF XY: 0.591 AC XY: 43913 AN XY: 74310

African (AFR) AF: 0.678 AC: 28128 AN: 41464

American (AMR) AF: 0.569 AC: 8698 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1888 AN: 3466

East Asian (EAS) AF: 0.848 AC: 4389 AN: 5174

South Asian (SAS) AF: 0.556 AC: 2682 AN: 4824

European-Finnish (FIN) AF: 0.502 AC: 5297 AN: 10546

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37651 AN: 67980

Other (OTH) AF: 0.599 AC: 1266 AN: 2112

Alfa AF: 0.568 Hom.: 109270

Bravo AF: 0.603

Asia WGS AF: 0.693 AC: 2411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.7
DANN	Benign	0.32
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4148557; hg19: chr3-183733784;