rs1016752

Variant summary

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

The ENST00000334444.11(ABCC5):​c.3414+50C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,508,722 control chromosomes in the GnomAD database, including 317,560 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 0.71 ( 40056 hom., cov: 30)
Exomes 𝑓: 0.63 ( 277504 hom. )

Consequence

ABCC5
ENST00000334444.11 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.92
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]

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=-0.94).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCC5NM_005688.4 linkuse as main transcriptc.3414+50C>G intron_variant ENST00000334444.11 NP_005679.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCC5ENST00000334444.11 linkuse as main transcriptc.3414+50C>G intron_variant 1 NM_005688.4 ENSP00000333926 P1O15440-1
ABCC5ENST00000265586.10 linkuse as main transcriptc.3285+50C>G intron_variant 5 ENSP00000265586 O15440-5
ABCC5ENST00000437205.5 linkuse as main transcriptc.*2107+50C>G intron_variant, NMD_transcript_variant 5 ENSP00000403510

Frequencies

GnomAD3 genomes
AF:
0.714
AC:
108293
AN:
151638
Hom.:
40001
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.901
Gnomad AMI
AF:
0.509
Gnomad AMR
AF:
0.702
Gnomad ASJ
AF:
0.720
Gnomad EAS
AF:
0.928
Gnomad SAS
AF:
0.602
Gnomad FIN
AF:
0.542
Gnomad MID
AF:
0.731
Gnomad NFE
AF:
0.624
Gnomad OTH
AF:
0.724
GnomAD3 exomes
AF:
0.669
AC:
113269
AN:
169422
Hom.:
38851
AF XY:
0.657
AC XY:
59906
AN XY:
91178
show subpopulations
Gnomad AFR exome
AF:
0.912
Gnomad AMR exome
AF:
0.670
Gnomad ASJ exome
AF:
0.718
Gnomad EAS exome
AF:
0.923
Gnomad SAS exome
AF:
0.599
Gnomad FIN exome
AF:
0.551
Gnomad NFE exome
AF:
0.626
Gnomad OTH exome
AF:
0.673
GnomAD4 exome
AF:
0.635
AC:
861524
AN:
1356966
Hom.:
277504
Cov.:
25
AF XY:
0.633
AC XY:
420696
AN XY:
664572
show subpopulations
Gnomad4 AFR exome
AF:
0.913
Gnomad4 AMR exome
AF:
0.677
Gnomad4 ASJ exome
AF:
0.720
Gnomad4 EAS exome
AF:
0.933
Gnomad4 SAS exome
AF:
0.588
Gnomad4 FIN exome
AF:
0.560
Gnomad4 NFE exome
AF:
0.619
Gnomad4 OTH exome
AF:
0.656
GnomAD4 genome
AF:
0.714
AC:
108407
AN:
151756
Hom.:
40056
Cov.:
30
AF XY:
0.708
AC XY:
52464
AN XY:
74130
show subpopulations
Gnomad4 AFR
AF:
0.901
Gnomad4 AMR
AF:
0.702
Gnomad4 ASJ
AF:
0.720
Gnomad4 EAS
AF:
0.929
Gnomad4 SAS
AF:
0.601
Gnomad4 FIN
AF:
0.542
Gnomad4 NFE
AF:
0.624
Gnomad4 OTH
AF:
0.729
Alfa
AF:
0.664
Hom.:
6325
Bravo
AF:
0.737
Asia WGS
AF:
0.783
AC:
2727
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.021
DANN
Benign
0.36
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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.

Other links and lift over

dbSNP: rs1016752; hg19: chr3-183665062; COSMIC: COSV55586874; COSMIC: COSV55586874; API