chr21-14356476-G-A

Variant names:

• chr21-14356476-G-A
• rs2403771
• ENST00000463099.1:n.3077-1255G>A

Variant summary

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

The ENST00000463099.1(ABCC13):​n.3077-1255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,072 control chromosomes in the GnomAD database, including 1,657 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 0.14 (1657 hom., cov: 32)
• Consequence: ABCC13 ENST00000463099.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 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.3077-1255G>A		intron_variant	Intron 23 of 27	6

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21302 AN: 151954 Hom.: 1656 Cov.: 32

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.00867

Gnomad SAS AF: 0.0804

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.140 AC: 21310 AN: 152072 Hom.: 1657 Cov.: 32 AF XY: 0.138 AC XY: 10254 AN XY: 74326

African (AFR) AF: 0.0937 AC: 3892 AN: 41516

American (AMR) AF: 0.118 AC: 1797 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3470

East Asian (EAS) AF: 0.00869 AC: 45 AN: 5176

South Asian (SAS) AF: 0.0811 AC: 391 AN: 4822

European-Finnish (FIN) AF: 0.178 AC: 1877 AN: 10546

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12227 AN: 67972

Other (OTH) AF: 0.143 AC: 300 AN: 2104

Alfa AF: 0.149 Hom.: 1027

Bravo AF: 0.132

Asia WGS AF: 0.0510 AC: 180 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.28
PhyloP100		0.026

Splicing

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

Other links and lift over

dbSNP: rs2403771; hg19: chr21-15728797;