12-21910317-CAAA-CAAAAA

Position:

• chr12-21910317-CAAA-CAAAAA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_020297.4(ABCC9):​c.1165-6_1165-5insTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00075 (0 hom.)
• Consequence: ABCC9 NM_020297.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-21910317-C-CAA is Benign according to our data. Variant chr12-21910317-C-CAA is described in ClinVar as [Likely_benign]. Clinvar id is 3040132.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0015 (178/118584) while in subpopulation AFR AF= 0.00534 (166/31108). AF 95% confidence interval is 0.00467. There are 0 homozygotes in gnomad4. There are 83 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC9	NM_020297.4	c.1165-6_1165-5insTT		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	c.1165-6_1165-5insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_020297.4	P4

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 177 AN: 118576 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000335

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000522

Gnomad FIN AF: 0.000152

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000716

Gnomad OTH AF: 0.000616

GnomAD4 exome AF: 0.000751 AC: 951 AN: 1267020 Hom.: 0 Cov.: 0 AF XY: 0.000830 AC XY: 525 AN XY: 632462

Gnomad4 AFR exome AF: 0.00413

Gnomad4 AMR exome AF: 0.00155

Gnomad4 ASJ exome AF: 0.00159

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.00221

Gnomad4 FIN exome AF: 0.000311

Gnomad4 NFE exome AF: 0.000504

Gnomad4 OTH exome AF: 0.000814

GnomAD4 genome AF: 0.00150 AC: 178 AN: 118584 Hom.: 0 Cov.: 0 AF XY: 0.00146 AC XY: 83 AN XY: 56940

Gnomad4 AFR AF: 0.00534

Gnomad4 AMR AF: 0.000335

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000526

Gnomad4 FIN AF: 0.000152

Gnomad4 NFE AF: 0.0000716

Gnomad4 OTH AF: 0.000613

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ABCC9-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 09, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35857705; hg19: chr12-22063251;