rs1411076886

Positions:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_020297.4(ABCC9):c.1165-5G>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 0.000659 in 1,270,118 control chromosomes in the GnomAD database, including 1 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 0.0035 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00066 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

ABCC9
NM_020297.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001579

Clinical Significance

Likely benign criteria provided, single submitter B:4

Conservation

PhyloP100: -0.270

Variant links:

Genes affected

ABCC9 (HGNC:60): (ATP binding cassette subfamily C member 9) 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 is thought to form ATP-sensitive potassium channels in cardiac, skeletal, and vascular and non-vascular smooth muscle. Protein structure suggests a role as the drug-binding channel-modulating subunit of the extra-pancreatic ATP-sensitive potassium channels. Mutations in this gene are associated with cardiomyopathy dilated type 1O. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2011]

ABCC9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-21910317-C-A is Benign according to our data. Variant chr12-21910317-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 464654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-21910317-C-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000659 (837/1270118) while in subpopulation AMR AF= 0.00359 (118/32890). AF 95% confidence interval is 0.00306. There are 1 homozygotes in gnomad4_exome. There are 461 alleles in male gnomad4_exome subpopulation. Median coverage is 27. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC9	NM_020297.4 linkuse as main transcript	c.1165-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261200.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC9	ENST00000261200.9 linkuse as main transcript	c.1165-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_020297.4	P4	O60706-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

414

AN:

117952

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00386

Gnomad AMI

AF:

0.00135

Gnomad AMR

AF:

0.00252

Gnomad ASJ

AF:

0.00182

Gnomad EAS

AF:

0.00363

Gnomad SAS

AF:

0.00367

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00476

Gnomad NFE

AF:

0.00259

Gnomad OTH

AF:

0.00433

GnomAD4 exome

AF:

0.000659

AC:

837

AN:

1270118

Hom.:

Cov.:

AF XY:

0.000727

AC XY:

461

AN XY:

634026

show subpopulations

Gnomad4 AFR exome

AF:

0.00193

Gnomad4 AMR exome

AF:

0.00359

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.00230

Gnomad4 SAS exome

AF:

0.00174

Gnomad4 FIN exome

AF:

0.00181

Gnomad4 NFE exome

AF:

0.000304

Gnomad4 OTH exome

AF:

0.000962

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00352

AC:

415

AN:

117962

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

216

AN XY:

56680

show subpopulations

Gnomad4 AFR

AF:

0.00392

Gnomad4 AMR

AF:

0.00252

Gnomad4 ASJ

AF:

0.00182

Gnomad4 EAS

AF:

0.00363

Gnomad4 SAS

AF:

0.00343

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.00259

Gnomad4 OTH

AF:

0.00431

Alfa

AF:

0.00278

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Dilated cardiomyopathy 1O

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.2

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0020

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