Variant 3-183982423-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0290

Variant links:

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]

ABCC5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.999+28G>A		intron_variant		ENST00000334444.11

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ABCC5	ENST00000334444.11 linkuse as main transcript	c.999+28G>A	intron_variant	1	NM_005688.4	P1	O15440-1
ABCC5	ENST00000265586.10 linkuse as main transcript	c.999+28G>A	intron_variant	5			O15440-5
ABCC5	ENST00000437205.5 linkuse as main transcript	c.999+28G>A	intron_variant, NMD_transcript_variant	5
ABCC5	ENST00000492216.1 linkuse as main transcript	n.550+28G>A	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

62406

AN:

151888

Hom.:

13435

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.373

AC XY:

268911

AN XY:

721576

show subpopulations

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.:

AF XY:

0.403

AC XY:

29934

AN XY:

74304

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over