Variant chr12-21925904-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020297.4(ABCC9):c.406+38A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 1,583,664 control chromosomes in the GnomAD database, including 303,770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32287 hom., cov: 31)

Exomes 𝑓: 0.61 ( 271483 hom. )

Consequence

ABCC9
NM_020297.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.350

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:

ABCC9 (HGNC:):

ABCC9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 12-21925904-T-G is Benign according to our data. Variant chr12-21925904-T-G is described in ClinVar as [Benign]. Clinvar id is 261217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC9	NM_020297.4 linkuse as main transcript	c.406+38A>C		intron_variant		ENST00000261200.9	NP_064693.2	O60706-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC9	ENST00000261200.9 linkuse as main transcript	c.406+38A>C		intron_variant		5	NM_020297.4	ENSP00000261200.4		O60706-2

Frequencies

GnomAD3 genomes

AF:

0.648

AC:

98441

AN:

151846

Hom.:

32249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.640

Gnomad AMR

AF:

0.605

Gnomad ASJ

AF:

0.749

Gnomad EAS

AF:

0.800

Gnomad SAS

AF:

0.683

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.788

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.667

GnomAD3 exomes

AF:

0.638

AC:

159733

AN:

250198

Hom.:

51833

AF XY:

0.644

AC XY:

87168

AN XY:

135438

show subpopulations

Gnomad AFR exome

AF:

0.708

Gnomad AMR exome

AF:

0.564

Gnomad ASJ exome

AF:

0.747

Gnomad EAS exome

AF:

0.794

Gnomad SAS exome

AF:

0.698

Gnomad FIN exome

AF:

0.598

Gnomad NFE exome

AF:

0.607

Gnomad OTH exome

AF:

0.653

GnomAD4 exome

AF:

0.613

AC:

877424

AN:

1431700

Hom.:

271483

Cov.:

AF XY:

0.617

AC XY:

440327

AN XY:

713742

show subpopulations

Gnomad4 AFR exome

AF:

0.707

Gnomad4 AMR exome

AF:

0.568

Gnomad4 ASJ exome

AF:

0.752

Gnomad4 EAS exome

AF:

0.779

Gnomad4 SAS exome

AF:

0.697

Gnomad4 FIN exome

AF:

0.596

Gnomad4 NFE exome

AF:

0.594

Gnomad4 OTH exome

AF:

0.644

GnomAD4 genome

AF:

0.648

AC:

98535

AN:

151964

Hom.:

32287

Cov.:

AF XY:

0.650

AC XY:

48256

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.711

Gnomad4 AMR

AF:

0.605

Gnomad4 ASJ

AF:

0.749

Gnomad4 EAS

AF:

0.799

Gnomad4 SAS

AF:

0.682

Gnomad4 FIN

AF:

0.603

Gnomad4 NFE

AF:

0.607

Gnomad4 OTH

AF:

0.671

Alfa

AF:

0.631

Hom.:

31327

Bravo

AF:

0.652

Asia WGS

AF:

0.714

AC:

2480

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Hypertrichotic osteochondrodysplasia Cantu type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.1

DANN

Benign

0.39

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