12-21910317-CAAA-C

Position:

• chr12-21910317-CAAA-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS1

The NM_020297.4(ABCC9):​c.1165-8_1165-6del 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 0.00041 in 1,383,166 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 Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000017 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: ABCC9 NM_020297.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• 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 -5 ACMG points.

• BP6: Variant 12-21910317-CAAA-C is Benign according to our data. Variant chr12-21910317-CAAA-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000447 (565/1264602) while in subpopulation AMR AF= 0.00156 (51/32732). AF 95% confidence interval is 0.00122. There are 0 homozygotes in gnomad4_exome. There are 286 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC9	NM_020297.4	c.1165-8_1165-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261200.9	NP_064693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC9	ENST00000261200.9	c.1165-8_1165-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_020297.4	ENSP00000261200	P4

Frequencies

GnomAD3 genomes AF: 0.0000169 AC: 2 AN: 118564 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000179

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000447 AC: 565 AN: 1264602 Hom.: 0 AF XY: 0.000453 AC XY: 286 AN XY: 631286

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00156

Gnomad4 ASJ exome AF: 0.000485

Gnomad4 EAS exome AF: 0.000253

Gnomad4 SAS exome AF: 0.000750

Gnomad4 FIN exome AF: 0.000780

Gnomad4 NFE exome AF: 0.000388

Gnomad4 OTH exome AF: 0.000398

GnomAD4 genome AF: 0.0000169 AC: 2 AN: 118564 Hom.: 0 Cov.: 0 AF XY: 0.0000176 AC XY: 1 AN XY: 56900

Gnomad4 AFR AF: 0.0000322

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000179

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs35857705; hg19: chr12-22063251;