Genetic Variant ABCC5:c.*1243A>G (chr3-183920057-T-C) – 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.*1243A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,546 control chromosomes in the GnomAD database, including 21,757 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 0.53 ( 21713 hom., cov: 33)

Exomes 𝑓: 0.44 ( 44 hom. )

Consequence

ABCC5
NM_005688.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.697

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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC5	NM_005688.4 link	c.*1243A>G		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 link	c.*1243A>G	3_prime_UTR_variant	Exon 30 of 30	1	NM_005688.4	ENSP00000333926.6	O15440-1
ABCC5	ENST00000265586 link	c.*1243A>G	3_prime_UTR_variant	Exon 29 of 29	5		ENSP00000265586.6	O15440-5
ABCC5	ENST00000437205.5 link	n.*4250A>G	non_coding_transcript_exon_variant	Exon 30 of 30	5		ENSP00000403510.1	F8WCY8
ABCC5	ENST00000437205.5 link	n.*4250A>G	3_prime_UTR_variant	Exon 30 of 30	5		ENSP00000403510.1	F8WCY8

Frequencies

GnomAD3 genomes

AF:

0.527

AC:

80027

AN:

151996

Hom.:

21678

Cov.:

show subpopulations

Gnomad AFR

AF:

0.661

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.441

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.486

Gnomad OTH

AF:

0.539

GnomAD4 exome

AF:

0.440

AC:

190

AN:

432

Hom.:

Cov.:

AF XY:

0.431

AC XY:

106

AN XY:

246

show subpopulations

Gnomad4 AFR exome

AC:

AN:

Gnomad4 AMR exome

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AF:

0.435

AC:

180

AN:

414

Gnomad4 NFE exome

AF:

0.583

AC:

AN:

Gnomad4 Remaining exome

AF:

0.500

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.527

AC:

80112

AN:

152114

Hom.:

21713

Cov.:

AF XY:

0.519

AC XY:

38579

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.661

AC:

0.660602

AN:

0.660602

Gnomad4 AMR

AF:

0.486

AC:

0.486384

AN:

0.486384

Gnomad4 ASJ

AF:

0.446

AC:

0.446367

AN:

0.446367

Gnomad4 EAS

AF:

0.503

AC:

0.503096

AN:

0.503096

Gnomad4 SAS

AF:

0.439

AC:

0.439419

AN:

0.439419

Gnomad4 FIN

AF:

0.400

AC:

0.400113

AN:

0.400113

Gnomad4 NFE

AF:

0.486

AC:

0.4861

AN:

0.4861

Gnomad4 OTH

AF:

0.543

AC:

0.542694

AN:

0.542694

Heterozygous variant carriers

1940

3880

5821

7761

9701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.498

Hom.:

83796

Bravo

AF:

0.538

Asia WGS

AF:

0.504

AC:

1756

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

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