21-25584436-C-T

Position:

• chr21-25584436-C-T

Variant summary

Our verdict is Benign. Variant got -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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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

Gnomad4 AFR AF: 0.0528

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0839 Hom.: 152

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2282471; hg19: chr21-26956748;