rs1283798

Positions:

• chr12-21868261-G-A
• chr12-21868261-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020297.4(ABCC9):​c.2199-3784C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,008 control chromosomes in the GnomAD database, including 8,447 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8447 hom., cov: 32)
• Consequence: ABCC9 NM_020297.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.36

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC9	NM_020297.4	c.2199-3784C>T		intron_variant		ENST00000261200.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC9	ENST00000261200.9	c.2199-3784C>T		intron_variant		5	NM_020297.4	P4
	ENST00000539874.1	n.332-1321G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50230 AN: 151890 Hom.: 8435 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50279 AN: 152008 Hom.: 8447 Cov.: 32 AF XY: 0.331 AC XY: 24615 AN XY: 74306

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.345

Alfa AF: 0.294 Hom.: 8321

Bravo AF: 0.343

Asia WGS AF: 0.383 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.048
DANN	Benign	0.84

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

Other links and lift over

dbSNP: rs1283798; hg19: chr12-22021195;