Genetic Variant NM_005688.4:c.129+7980C>T (chr3-184006284-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005688.4(ABCC5):c.129+7980C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 140,368 control chromosomes in the GnomAD database, including 1,336 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 0.13 ( 1336 hom., cov: 27)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

ABCC5
NM_005688.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.23

Publications

9 publications found

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:

ABCC5-AS1 (HGNC:40055): (ABCC5 antisense RNA 1)

ABCC5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC5	NM_005688.4 link	c.129+7980C>T		intron_variant	Intron 2 of 29	ENST00000334444.11	NP_005679.2	O15440-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444.11 link	c.129+7980C>T		intron_variant	Intron 2 of 29	1	NM_005688.4	ENSP00000333926.6		O15440-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

18099

AN:

140270

Hom.:

1325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0887

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.0778

Gnomad EAS

AF:

0.360

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.0753

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.134

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.129

AC:

18127

AN:

140360

Hom.:

1336

Cov.:

AF XY:

0.133

AC XY:

8994

AN XY:

67470

show subpopulations

African (AFR)

AF:

0.0886

AC:

3225

AN:

36392

American (AMR)

AF:

0.205

AC:

2821

AN:

13752

Ashkenazi Jewish (ASJ)

AF:

0.0778

AC:

264

AN:

3394

East Asian (EAS)

AF:

0.360

AC:

1699

AN:

4720

South Asian (SAS)

AF:

0.137

AC:

597

AN:

4370

European-Finnish (FIN)

AF:

0.138

AC:

1167

AN:

8482

Middle Eastern (MID)

AF:

0.0704

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.119

AC:

7905

AN:

66174

Other (OTH)

AF:

0.143

AC:

272

AN:

1904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

732

1464

2197

2929

3661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.119

Hom.:

3445

Bravo

AF:

0.127

Asia WGS

AF:

0.239

AC:

831

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over