3-183982423-C-T

Variant names:

• chr3-183982423-C-T
• rs2293001
• NM_005688.4:c.999+28G>A

Variant summary

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

The NM_005688.4(ABCC5):​c.999+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,603,764 control chromosomes in the GnomAD database, including 116,039 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 0.41 (13444 hom., cov: 32)
  • Exomes 𝑓: 0.37 (102595 hom.)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 20 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC5	NM_005688.4	c.999+28G>A		intron_variant	Intron 7 of 29	ENST00000334444.11	NP_005679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444.11	c.999+28G>A		intron_variant	Intron 7 of 29	1	NM_005688.4	ENSP00000333926.6
ABCC5	ENST00000265586.10	c.999+28G>A		intron_variant	Intron 7 of 28	5		ENSP00000265586.6
ABCC5	ENST00000437205.5	n.999+28G>A		intron_variant	Intron 7 of 29	5		ENSP00000403510.1
ABCC5	ENST00000492216.1	n.550+28G>A		intron_variant	Intron 3 of 5	5

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62406 AN: 151888 Hom.: 13435 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.411

GnomAD2 exomes AF: 0.364 AC: 87879 AN: 241474 AF XY: 0.364

Gnomad AFR exome AF: 0.552

Gnomad AMR exome AF: 0.281

Gnomad ASJ exome AF: 0.411

Gnomad EAS exome AF: 0.411

Gnomad FIN exome AF: 0.277

Gnomad NFE exome AF: 0.368

Gnomad OTH exome AF: 0.367

GnomAD4 exome AF: 0.373 AC: 541699 AN: 1451758 Hom.: 102595 Cov.: 33 AF XY: 0.373 AC XY: 268911 AN XY: 721576

African (AFR) AF: 0.552 AC: 18272 AN: 33108

American (AMR) AF: 0.287 AC: 12580 AN: 43840

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 10391 AN: 25628

East Asian (EAS) AF: 0.463 AC: 18308 AN: 39532

South Asian (SAS) AF: 0.361 AC: 30791 AN: 85210

European-Finnish (FIN) AF: 0.284 AC: 15117 AN: 53142

Middle Eastern (MID) AF: 0.413 AC: 2234 AN: 5412

European-Non Finnish (NFE) AF: 0.372 AC: 411373 AN: 1106014

Other (OTH) AF: 0.378 AC: 22633 AN: 59872

GnomAD4 genome AF: 0.411 AC: 62435 AN: 152006 Hom.: 13444 Cov.: 32 AF XY: 0.403 AC XY: 29934 AN XY: 74304

African (AFR) AF: 0.543 AC: 22518 AN: 41458

American (AMR) AF: 0.332 AC: 5073 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1432 AN: 3466

East Asian (EAS) AF: 0.425 AC: 2196 AN: 5166

South Asian (SAS) AF: 0.373 AC: 1797 AN: 4814

European-Finnish (FIN) AF: 0.274 AC: 2893 AN: 10568

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25291 AN: 67960

Other (OTH) AF: 0.407 AC: 859 AN: 2112

Alfa AF: 0.393 Hom.: 39585

Bravo AF: 0.419

Asia WGS AF: 0.405 AC: 1408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.1
DANN	Benign	0.62
PhyloP100		0.029
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: rs2293001; hg19: chr3-183700211; COSMIC: COSV55597878; COSMIC: COSV55597878;