rs2313212

Variant summary

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

The NM_005688.4(ABCC5):​c.592-133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 773,806 control chromosomes in the GnomAD database, including 134,717 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 0.62 ( 30462 hom., cov: 33)
Exomes 𝑓: 0.57 ( 104255 hom. )

Consequence

ABCC5
NM_005688.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0150
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCC5NM_005688.4 linkuse as main transcriptc.592-133T>C intron_variant ENST00000334444.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCC5ENST00000334444.11 linkuse as main transcriptc.592-133T>C intron_variant 1 NM_005688.4 P1O15440-1
ABCC5ENST00000265586.10 linkuse as main transcriptc.592-133T>C intron_variant 5 O15440-5
ABCC5ENST00000437205.5 linkuse as main transcriptc.592-133T>C intron_variant, NMD_transcript_variant 5
ABCC5ENST00000492216.1 linkuse as main transcriptn.143-133T>C intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.623
AC:
94781
AN:
152052
Hom.:
30418
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.766
Gnomad AMI
AF:
0.459
Gnomad AMR
AF:
0.583
Gnomad ASJ
AF:
0.551
Gnomad EAS
AF:
0.852
Gnomad SAS
AF:
0.557
Gnomad FIN
AF:
0.501
Gnomad MID
AF:
0.595
Gnomad NFE
AF:
0.558
Gnomad OTH
AF:
0.631
GnomAD4 exome
AF:
0.573
AC:
356042
AN:
621636
Hom.:
104255
AF XY:
0.571
AC XY:
183795
AN XY:
321948
show subpopulations
Gnomad4 AFR exome
AF:
0.766
Gnomad4 AMR exome
AF:
0.546
Gnomad4 ASJ exome
AF:
0.549
Gnomad4 EAS exome
AF:
0.854
Gnomad4 SAS exome
AF:
0.543
Gnomad4 FIN exome
AF:
0.511
Gnomad4 NFE exome
AF:
0.554
Gnomad4 OTH exome
AF:
0.581
GnomAD4 genome
AF:
0.623
AC:
94876
AN:
152170
Hom.:
30462
Cov.:
33
AF XY:
0.618
AC XY:
45939
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.766
Gnomad4 AMR
AF:
0.583
Gnomad4 ASJ
AF:
0.551
Gnomad4 EAS
AF:
0.853
Gnomad4 SAS
AF:
0.555
Gnomad4 FIN
AF:
0.501
Gnomad4 NFE
AF:
0.558
Gnomad4 OTH
AF:
0.637
Alfa
AF:
0.569
Hom.:
49969
Bravo
AF:
0.635
Asia WGS
AF:
0.725
AC:
2523
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.71
DANN
Benign
0.47

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: rs2313212; hg19: chr3-183700928; API