Variant chr17-50655826-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003786.4(ABCC3):c.46-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00581 in 1,613,600 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0059 ( 33 hom. )

Consequence

ABCC3
NM_003786.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002854

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.667

Variant links:

Genes affected

ABCC3 (HGNC:54): (ATP binding cassette subfamily C member 3) 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. The specific function of this protein has not yet been determined; however, this protein may play a role in the transport of biliary and intestinal excretion of organic anions. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ABCC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 17-50655826-C-T is Benign according to our data. Variant chr17-50655826-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647940.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC3	NM_003786.4 linkuse as main transcript	c.46-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000285238.13
ABCC3	NM_001144070.2 linkuse as main transcript	c.46-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC3	ENST00000285238.13 linkuse as main transcript	c.46-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003786.4	P1	O15438-1

Frequencies

GnomAD3 genomes

AF:

0.00482

AC:

734

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00663

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00519

AC:

1301

AN:

250520

Hom.:

AF XY:

0.00509

AC XY:

689

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.00631

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.00753

Gnomad OTH exome

AF:

0.00425

GnomAD4 exome

AF:

0.00591

AC:

8641

AN:

1461350

Hom.:

Cov.:

AF XY:

0.00581

AC XY:

4223

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.00239

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.00603

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.00893

Gnomad4 NFE exome

AF:

0.00670

Gnomad4 OTH exome

AF:

0.00500

GnomAD4 genome

AF:

0.00483

AC:

736

AN:

152250

Hom.:

Cov.:

AF XY:

0.00489

AC XY:

364

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.00663

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00404

Hom.:

Bravo

AF:

0.00419

EpiCase

AF:

0.00699

EpiControl

AF:

0.00717

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

ABCC3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.9

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00029

dbscSNV1_RF

Benign

0.070

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