12-21840544-G-C

Variant names:

• chr12-21840544-G-C
• rs704178
• NM_020297.4:c.3473+1770C>G

Variant summary

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

The NM_020297.4(ABCC9):​c.3473+1770C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,004 control chromosomes in the GnomAD database, including 23,546 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 0.55 (23546 hom., cov: 33)
• Consequence: ABCC9 NM_020297.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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]

ENSG00000257022 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC9	NM_020297.4	c.3473+1770C>G		intron_variant	Intron 29 of 39	ENST00000261200.9	NP_064693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC9	ENST00000261200.9	c.3473+1770C>G		intron_variant	Intron 29 of 39	5	NM_020297.4	ENSP00000261200.4

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83146 AN: 151886 Hom.: 23528 Cov.: 33

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.547 AC: 83206 AN: 152004 Hom.: 23546 Cov.: 33 AF XY: 0.543 AC XY: 40345 AN XY: 74266

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.540

Alfa AF: 0.363 Hom.: 877

Bravo AF: 0.571

Asia WGS AF: 0.508 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.69

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: rs704178; hg19: chr12-21993478;