Genetic Variant ABCC9:c.4450-5dupT (chr12-21806064-C-CA) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_020297.4(ABCC9):c.4450-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 1,073,430 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., cov: 32)

Exomes 𝑓: 0.099 ( 0 hom. )

Consequence

ABCC9
NM_020297.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.729

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:

LOC105369689 (HGNC:):

LOC105369689 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-21806064-C-CA is Benign according to our data. Variant chr12-21806064-C-CA is described in ClinVar as [Benign]. Clinvar id is 178859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC9	NM_020297.4 link	c.4450-5dupT		splice_region_variant, intron_variant	Intron 38 of 39	ENST00000261200.9	NP_064693.2	O60706-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC9	ENST00000261200.9 link	c.4450-5_4450-4insT		splice_region_variant, intron_variant	Intron 38 of 39	5	NM_020297.4	ENSP00000261200.4		O60706-2

Frequencies

GnomAD3 genomes

AF:

0.000925

AC:

130

AN:

140582

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000984

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00122

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000611

Gnomad SAS

AF:

0.00111

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00336

Gnomad NFE

AF:

0.000624

Gnomad OTH

AF:

0.00157

GnomAD4 exome

AF:

0.0986

AC:

92015

AN:

932776

Hom.:

Cov.:

AF XY:

0.0954

AC XY:

44216

AN XY:

463548

show subpopulations

Gnomad4 AFR exome

AF:

0.0848

Gnomad4 AMR exome

AF:

0.0696

Gnomad4 ASJ exome

AF:

0.0902

Gnomad4 EAS exome

AF:

0.0971

Gnomad4 SAS exome

AF:

0.0646

Gnomad4 FIN exome

AF:

0.0810

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0996

GnomAD4 genome

AF:

0.000931

AC:

131

AN:

140654

Hom.:

Cov.:

AF XY:

0.000911

AC XY:

AN XY:

68034

show subpopulations

Gnomad4 AFR

AF:

0.000982

Gnomad4 AMR

AF:

0.00122

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000613

Gnomad4 SAS

AF:

0.00111

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.000624

Gnomad4 OTH

AF:

0.00207

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 05, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1O

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiomyopathy

Benign:1

May 30, 2019

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

12-21806064-CAAA-CAAAA

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