3-183967461-T-C

Variant names:

• chr3-183967461-T-C
• rs4148579
• NM_005688.4:c.1833+234A>G

Variant summary

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

The NM_005688.4(ABCC5):​c.1833+234A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 493,864 control chromosomes in the GnomAD database, including 88,856 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 (31054 hom., cov: 31)
  • Exomes 𝑓: 0.57 (57802 hom.)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.664
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC5	NM_005688.4	c.1833+234A>G		intron_variant	Intron 12 of 29	ENST00000334444.11	NP_005679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444.11	c.1833+234A>G		intron_variant	Intron 12 of 29	1	NM_005688.4	ENSP00000333926.6
ABCC5	ENST00000476402.1	n.575A>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
ABCC5	ENST00000265586.10	c.1833+234A>G		intron_variant	Intron 12 of 28	5		ENSP00000265586.6
ABCC5	ENST00000437205.5	n.*526+234A>G		intron_variant	Intron 12 of 29	5		ENSP00000403510.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95541 AN: 151894 Hom.: 31006 Cov.: 31

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.635

GnomAD4 exome AF: 0.573 AC: 195752 AN: 341852 Hom.: 57802 Cov.: 3 AF XY: 0.570 AC XY: 103976 AN XY: 182282

African (AFR) AF: 0.778 AC: 7593 AN: 9754

American (AMR) AF: 0.548 AC: 8452 AN: 15410

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 5545 AN: 10068

East Asian (EAS) AF: 0.864 AC: 18379 AN: 21284

South Asian (SAS) AF: 0.546 AC: 23981 AN: 43926

European-Finnish (FIN) AF: 0.502 AC: 9848 AN: 19602

Middle Eastern (MID) AF: 0.608 AC: 847 AN: 1392

European-Non Finnish (NFE) AF: 0.547 AC: 110018 AN: 201076

Other (OTH) AF: 0.573 AC: 11089 AN: 19340

GnomAD4 genome AF: 0.629 AC: 95641 AN: 152012 Hom.: 31054 Cov.: 31 AF XY: 0.623 AC XY: 46280 AN XY: 74276

African (AFR) AF: 0.783 AC: 32507 AN: 41500

American (AMR) AF: 0.585 AC: 8933 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1916 AN: 3470

East Asian (EAS) AF: 0.861 AC: 4442 AN: 5158

South Asian (SAS) AF: 0.560 AC: 2697 AN: 4812

European-Finnish (FIN) AF: 0.500 AC: 5277 AN: 10546

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37926 AN: 67954

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

Alfa AF: 0.576 Hom.: 41541

Bravo AF: 0.642

Asia WGS AF: 0.731 AC: 2543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		-0.66
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: rs4148579; hg19: chr3-183685249;