Genetic Variant NM_005688.4:c.*582G>A (chr3-183920718-C-T) – 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.*582G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,482 control chromosomes in the GnomAD database, including 12,864 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 0.39 ( 12819 hom., cov: 32)

Exomes 𝑓: 0.43 ( 45 hom. )

Consequence

ABCC5
NM_005688.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.751

Publications

11 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:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC5	NM_005688.4 link	c.*582G>A		3_prime_UTR_variant	Exon 30 of 30	ENST00000334444.11	NP_005679.2	O15440-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCC5	ENST00000334444.11 link	c.*582G>A	3_prime_UTR_variant	Exon 30 of 30	1	NM_005688.4	ENSP00000333926.6	O15440-1
ABCC5	ENST00000437205.5 link	n.*3589G>A	non_coding_transcript_exon_variant	Exon 30 of 30	5		ENSP00000403510.1	F8WCY8
ABCC5	ENST00000265586.10 link	c.*582G>A	3_prime_UTR_variant	Exon 29 of 29	5		ENSP00000265586.6	O15440-5
ABCC5	ENST00000437205.5 link	n.*3589G>A	3_prime_UTR_variant	Exon 30 of 30	5		ENSP00000403510.1	F8WCY8

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

59011

AN:

151926

Hom.:

12812

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.436

Gnomad ASJ

AF:

0.433

Gnomad EAS

AF:

0.502

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.437

GnomAD4 exome

AF:

0.433

AC:

189

AN:

436

Hom.:

Cov.:

AF XY:

0.410

AC XY:

109

AN XY:

266

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.434

AC:

171

AN:

394

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.469

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.388

AC:

59038

AN:

152046

Hom.:

12819

Cov.:

AF XY:

0.387

AC XY:

28732

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.182

AC:

7554

AN:

41494

American (AMR)

AF:

0.436

AC:

6661

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

1502

AN:

3468

East Asian (EAS)

AF:

0.503

AC:

2594

AN:

5162

South Asian (SAS)

AF:

0.435

AC:

2095

AN:

4814

European-Finnish (FIN)

AF:

0.400

AC:

4226

AN:

10558

Middle Eastern (MID)

AF:

0.490

AC:

143

AN:

292

European-Non Finnish (NFE)

AF:

0.484

AC:

32914

AN:

67956

Other (OTH)

AF:

0.441

AC:

932

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1735

3469

5204

6938

8673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.405

Hom.:

1762

Bravo

AF:

0.382

Asia WGS

AF:

0.471

AC:

1638

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

0.60

(source)

DANN

Benign

0.63

PhyloP100

-0.75

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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