rs1411076886

Variant names:

• chr12-21910317-C-A
• rs1411076886
• NM_020297.4:c.1165-5G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-21910317-C-A
• chr12-21910317-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_020297.4(ABCC9):​c.1165-5G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000659 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, intron
• Scores: Splicing: ADA: 0.00001579
• Clinical Significance: Likely benign criteria provided, single submitter B:4
• Conservation: PhyloP100: -0.270

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]

ACMG classification

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 rank	MANE	Protein	UniProt
ABCC9	NM_020297.4	c.1165-5G>T		splice_region_variant, intron_variant	Intron 9 of 39	ENST00000261200.9	NP_064693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC9	ENST00000261200.9	c.1165-5G>T		splice_region_variant, intron_variant	Intron 9 of 39	5	NM_020297.4	ENSP00000261200.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 414 AN: 117952 Hom.: 0 Cov.: 23 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.: 1 Cov.: 27 AF XY: 0.000727 AC XY: 461 AN XY: 634026

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.: 0 Cov.: 23 AF XY: 0.00381 AC XY: 216 AN XY: 56680

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.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:3

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

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

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1O Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Other links and lift over

dbSNP: rs1411076886; hg19: chr12-22063251;