12-21861539-G-A

Position:

• chr12-21861539-G-A

Variant summary

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

The NM_020297.4(ABCC9):​c.2340-484C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,870 control chromosomes in the GnomAD database, including 28,431 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 0.61 (28431 hom., cov: 31)
• Consequence: ABCC9 NM_020297.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC9	NM_020297.4	c.2340-484C>T		intron_variant		ENST00000261200.9	NP_064693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC9	ENST00000261200.9	c.2340-484C>T		intron_variant		5	NM_020297.4	ENSP00000261200	P4
	ENST00000539874.1	n.332-8043G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92099 AN: 151752 Hom.: 28422 Cov.: 31

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.607 AC: 92149 AN: 151870 Hom.: 28431 Cov.: 31 AF XY: 0.608 AC XY: 45140 AN XY: 74186

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.593

Alfa AF: 0.564 Hom.: 22896

Bravo AF: 0.616

Asia WGS AF: 0.617 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.66
DANN	Benign	0.96

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: rs704190; hg19: chr12-22014473;