Variant rs939336 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005688.4(ABCC5):c.1782T>C(p.Cys594=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,611,950 control chromosomes in the GnomAD database, including 267,442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30499 hom., cov: 32)

Exomes 𝑓: 0.57 ( 236943 hom. )

Consequence

ABCC5
NM_005688.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.150

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 3-183967746-A-G is Benign according to our data. Variant chr3-183967746-A-G is described in ClinVar as [Benign]. Clinvar id is 1252281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC5	NM_005688.4 linkuse as main transcript	c.1782T>C	p.Cys594=	synonymous_variant	12/30	ENST00000334444.11	NP_005679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444.11 linkuse as main transcript	c.1782T>C	p.Cys594=	synonymous_variant	12/30	1	NM_005688.4	ENSP00000333926	P1	O15440-1
ABCC5	ENST00000265586.10 linkuse as main transcript	c.1782T>C	p.Cys594=	synonymous_variant	12/29	5		ENSP00000265586		O15440-5
ABCC5	ENST00000476402.1 linkuse as main transcript	n.290T>C		non_coding_transcript_exon_variant	2/2	2
ABCC5	ENST00000437205.5 linkuse as main transcript	c.*475T>C		3_prime_UTR_variant, NMD_transcript_variant	12/30	5		ENSP00000403510

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94823

AN:

151996

Hom.:

30455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.860

Gnomad SAS

AF:

0.563

Gnomad FIN

AF:

0.501

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.631

GnomAD3 exomes

AF:

0.582

AC:

145318

AN:

249500

Hom.:

43691

AF XY:

0.576

AC XY:

77995

AN XY:

135370

show subpopulations

Gnomad AFR exome

AF:

0.780

Gnomad AMR exome

AF:

0.524

Gnomad ASJ exome

AF:

0.550

Gnomad EAS exome

AF:

0.859

Gnomad SAS exome

AF:

0.552

Gnomad FIN exome

AF:

0.502

Gnomad NFE exome

AF:

0.556

Gnomad OTH exome

AF:

0.582

GnomAD4 exome

AF:

0.566

AC:

825669

AN:

1459836

Hom.:

236943

Cov.:

AF XY:

0.564

AC XY:

409949

AN XY:

726342

show subpopulations

Gnomad4 AFR exome

AF:

0.774

Gnomad4 AMR exome

AF:

0.531

Gnomad4 ASJ exome

AF:

0.552

Gnomad4 EAS exome

AF:

0.864

Gnomad4 SAS exome

AF:

0.546

Gnomad4 FIN exome

AF:

0.510

Gnomad4 NFE exome

AF:

0.554

Gnomad4 OTH exome

AF:

0.577

GnomAD4 genome

AF:

0.624

AC:

94919

AN:

152114

Hom.:

30499

Cov.:

AF XY:

0.618

AC XY:

45943

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.766

Gnomad4 AMR

AF:

0.583

Gnomad4 ASJ

AF:

0.551

Gnomad4 EAS

AF:

0.861

Gnomad4 SAS

AF:

0.561

Gnomad4 FIN

AF:

0.501

Gnomad4 NFE

AF:

0.558

Gnomad4 OTH

AF:

0.637

Alfa

AF:

0.573

Hom.:

59637

Bravo

AF:

0.636

Asia WGS

AF:

0.730

AC:

2539

AN:

3478

EpiCase

AF:

0.564

EpiControl

AF:

0.577

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 27, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.2

DANN

Benign

0.52

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over