rs4762719

Positions:

• chr12-21910803-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_020297.4(ABCC9):​c.1164+23A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,594,076 control chromosomes in the GnomAD database, including 42 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 0.0092 (23 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (19 hom.)
• Consequence: ABCC9 NM_020297.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=2.786).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0092 (1398/152004) while in subpopulation AFR AF= 0.0312 (1294/41502). AF 95% confidence interval is 0.0298. There are 23 homozygotes in gnomad4. There are 663 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC9	NM_020297.4	c.1164+23A>C		intron_variant		ENST00000261200.9	NP_064693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC9	ENST00000261200.9	c.1164+23A>C		intron_variant		5	NM_020297.4	ENSP00000261200	P4

Frequencies

GnomAD3 genomes AF: 0.00910 AC: 1382 AN: 151886 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00434

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.000933 AC: 1345 AN: 1442072 Hom.: 19 Cov.: 28 AF XY: 0.000836 AC XY: 601 AN XY: 718806

Gnomad4 AFR exome AF: 0.0297

Gnomad4 AMR exome AF: 0.00258

Gnomad4 ASJ exome AF: 0.000425

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000816

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000941

Gnomad4 OTH exome AF: 0.00206

GnomAD4 genome AF: 0.00920 AC: 1398 AN: 152004 Hom.: 23 Cov.: 32 AF XY: 0.00892 AC XY: 663 AN XY: 74328

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.00434

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000236

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.00351 Hom.: 1

Bravo AF: 0.0101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	2.8

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4762719; hg19: -;