3-183984487-A-G

Variant names:

• chr3-183984487-A-G
• rs4148575
• ENST00000443376.5:n.*512T>C

Variant summary

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

The ENST00000443376.5(ABCC5):​n.*512T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,050,148 control chromosomes in the GnomAD database, including 169,972 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 0.61 (29180 hom., cov: 30)
  • Exomes 𝑓: 0.56 (140792 hom.)
• Consequence: ABCC5 ENST00000443376.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 22 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC5	NM_005688.4	c.592-1480T>C		intron_variant	Intron 5 of 29	ENST00000334444.11	NP_005679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444.11	c.592-1480T>C		intron_variant	Intron 5 of 29	1	NM_005688.4	ENSP00000333926.6

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93000 AN: 151760 Hom.: 29151 Cov.: 30

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.558 AC: 501038 AN: 898270 Hom.: 140792 Cov.: 34 AF XY: 0.556 AC XY: 233264 AN XY: 419188

African (AFR) AF: 0.734 AC: 12816 AN: 17468

American (AMR) AF: 0.557 AC: 2640 AN: 4736

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 3891 AN: 7008

East Asian (EAS) AF: 0.855 AC: 6021 AN: 7038

South Asian (SAS) AF: 0.531 AC: 13288 AN: 25014

European-Finnish (FIN) AF: 0.487 AC: 1357 AN: 2784

Middle Eastern (MID) AF: 0.581 AC: 1081 AN: 1860

European-Non Finnish (NFE) AF: 0.552 AC: 442507 AN: 801524

Other (OTH) AF: 0.565 AC: 17437 AN: 30838

GnomAD4 genome AF: 0.613 AC: 93079 AN: 151878 Hom.: 29180 Cov.: 30 AF XY: 0.608 AC XY: 45102 AN XY: 74230

African (AFR) AF: 0.725 AC: 30045 AN: 41420

American (AMR) AF: 0.588 AC: 8964 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1913 AN: 3472

East Asian (EAS) AF: 0.853 AC: 4402 AN: 5160

South Asian (SAS) AF: 0.554 AC: 2668 AN: 4814

European-Finnish (FIN) AF: 0.502 AC: 5284 AN: 10534

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

European-Non Finnish (NFE) AF: 0.558 AC: 37886 AN: 67912

Other (OTH) AF: 0.628 AC: 1325 AN: 2110

Alfa AF: 0.578 Hom.: 81167

Bravo AF: 0.625

Asia WGS AF: 0.709 AC: 2466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.46
PhyloP100		1.9
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: rs4148575; hg19: chr3-183702275;