3-183952854-A-G

Variant names:

• chr3-183952854-A-G
• rs4148585
• NM_005688.4:c.2667+232T>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.2667+232T>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 151,976 control chromosomes in the GnomAD database, including 31,091 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 (31091 hom., cov: 31)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• Publications: 13 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=-0.93).
• 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.2667+232T>C		intron_variant	Intron 18 of 29	ENST00000334444.11	NP_005679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444.11	c.2667+232T>C		intron_variant	Intron 18 of 29	1	NM_005688.4	ENSP00000333926.6
ABCC5	ENST00000265586.10	c.2667+232T>C		intron_variant	Intron 18 of 28	5		ENSP00000265586.6
ABCC5	ENST00000437205.5	n.*1360+232T>C		intron_variant	Intron 18 of 29	5		ENSP00000403510.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95572 AN: 151856 Hom.: 31038 Cov.: 31

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.630 AC: 95681 AN: 151976 Hom.: 31091 Cov.: 31 AF XY: 0.624 AC XY: 46319 AN XY: 74280

African (AFR) AF: 0.785 AC: 32568 AN: 41500

American (AMR) AF: 0.586 AC: 8949 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1910 AN: 3462

East Asian (EAS) AF: 0.861 AC: 4443 AN: 5160

South Asian (SAS) AF: 0.561 AC: 2704 AN: 4816

European-Finnish (FIN) AF: 0.501 AC: 5285 AN: 10544

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37878 AN: 67908

Other (OTH) AF: 0.641 AC: 1351 AN: 2106

Alfa AF: 0.578 Hom.: 41421

Bravo AF: 0.643

Asia WGS AF: 0.732 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.2
DANN	Benign	0.52
PhyloP100		0.51
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: rs4148585; hg19: chr3-183670642;