21-25584436-C-T

Variant names:

• chr21-25584436-C-T
• rs2282471

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 0.127 in 151,820 control chromosomes in the GnomAD database, including 1,607 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 0.13 (1607 hom., cov: 31)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 9 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 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: 0.127 AC: 19232 AN: 151698 Hom.: 1596 Cov.: 31

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.127 AC: 19262 AN: 151820 Hom.: 1607 Cov.: 31 AF XY: 0.136 AC XY: 10069 AN XY: 74174

African (AFR) AF: 0.0528 AC: 2187 AN: 41442

American (AMR) AF: 0.175 AC: 2662 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1248 AN: 5136

South Asian (SAS) AF: 0.322 AC: 1545 AN: 4802

European-Finnish (FIN) AF: 0.169 AC: 1769 AN: 10488

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8916 AN: 67922

Other (OTH) AF: 0.129 AC: 273 AN: 2114

Alfa AF: 0.0833 Hom.: 154

Bravo AF: 0.120

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.81
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs2282471; hg19: chr21-26956748;