chr3-183982423-C-T

Position:

• chr3-183982423-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ABCC5	NM_005688.4	c.999+28G>A		intron_variant		ENST00000334444.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC5	ENST00000334444.11	c.999+28G>A		intron_variant		1	NM_005688.4	P1
ABCC5	ENST00000265586.10	c.999+28G>A		intron_variant		5
ABCC5	ENST00000437205.5	c.999+28G>A		intron_variant, NMD_transcript_variant		5
ABCC5	ENST00000492216.1	n.550+28G>A		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.364 AC: 87879 AN: 241474 Hom.: 16562 AF XY: 0.364 AC XY: 47764 AN XY: 131204

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 SAS exome AF: 0.366

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

Gnomad4 AFR exome AF: 0.552

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.405

Gnomad4 EAS exome AF: 0.463

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 0.378

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

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.407

Alfa AF: 0.385 Hom.: 16493

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2293001; hg19: chr3-183700211; COSMIC: COSV55597878; COSMIC: COSV55597878;