rs2822618

Variant names:

• chr21-14353547-G-A
• rs2822618
• ENST00000463099.1:n.2848-7G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000463099.1(ABCC13):​n.2848-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,444 control chromosomes in the GnomAD database, including 24,963 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 0.57 (24905 hom., cov: 32)
  • Exomes 𝑓: 0.52 (58 hom.)
• Consequence: ABCC13 ENST00000463099.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 3 publications found

Genes affected

ABCC13 (HGNC:16022): (ATP binding cassette subfamily C member 13 (pseudogene)) This gene is a member of the superfamily of genes encoding 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, and White). This family member is part of the MRP subfamily, which is involved in multi-drug resistance, but the human locus is now thought to be a pseudogene incapable of encoding a functional ABC protein. Alternative splicing results in multiple transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC13	ENST00000463099.1	n.2848-7G>A		splice_region_variant, intron_variant	Intron 21 of 27	6

Frequencies

GnomAD3 genomes AF: 0.566 AC: 86008 AN: 151890 Hom.: 24870 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 0.518 AC: 226 AN: 436 Hom.: 58 Cov.: 0 AF XY: 0.477 AC XY: 126 AN XY: 264

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.514 AC: 219 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 4 AN: 6

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.566 AC: 86088 AN: 152008 Hom.: 24905 Cov.: 32 AF XY: 0.563 AC XY: 41795 AN XY: 74296

African (AFR) AF: 0.691 AC: 28667 AN: 41466

American (AMR) AF: 0.516 AC: 7881 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2042 AN: 3468

East Asian (EAS) AF: 0.594 AC: 3075 AN: 5174

South Asian (SAS) AF: 0.527 AC: 2541 AN: 4826

European-Finnish (FIN) AF: 0.473 AC: 4997 AN: 10562

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34982 AN: 67930

Other (OTH) AF: 0.585 AC: 1234 AN: 2110

Alfa AF: 0.533 Hom.: 94119

Bravo AF: 0.576

Asia WGS AF: 0.608 AC: 2115 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	0.42
DANN	Benign	0.24
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs2822618; hg19: chr21-15725868;