rs2183589

Variant names:

• chr21-45401576-C-T
• rs2183589

Variant summary

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

The variant allele was found at a frequency of 0.16 in 152,122 control chromosomes in the GnomAD database, including 2,521 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 0.16 (2521 hom., cov: 33)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924
• Publications: 9 publications found

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 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

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24347 AN: 152004 Hom.: 2506 Cov.: 33

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.160 AC: 24397 AN: 152122 Hom.: 2521 Cov.: 33 AF XY: 0.162 AC XY: 12016 AN XY: 74366

African (AFR) AF: 0.282 AC: 11699 AN: 41456

American (AMR) AF: 0.0873 AC: 1334 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3470

East Asian (EAS) AF: 0.147 AC: 762 AN: 5184

South Asian (SAS) AF: 0.181 AC: 872 AN: 4820

European-Finnish (FIN) AF: 0.169 AC: 1791 AN: 10572

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7286 AN: 68020

Other (OTH) AF: 0.134 AC: 284 AN: 2114

Alfa AF: 0.115 Hom.: 1999

Bravo AF: 0.156

Asia WGS AF: 0.146 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.29
PhyloP100		-0.92

Splicing

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

Other links and lift over

dbSNP: rs2183589; hg19: chr21-46821491;