chr21-25859887-G-A

Variant names:

• chr21-25859887-G-A
• rs2040273

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 0.65 in 151,944 control chromosomes in the GnomAD database, including 32,732 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 0.65 (32732 hom., cov: 31)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 8 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 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: 0.649 AC: 98582 AN: 151826 Hom.: 32674 Cov.: 31

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.650 AC: 98703 AN: 151944 Hom.: 32732 Cov.: 31 AF XY: 0.653 AC XY: 48482 AN XY: 74264

African (AFR) AF: 0.781 AC: 32344 AN: 41432

American (AMR) AF: 0.654 AC: 9983 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1993 AN: 3470

East Asian (EAS) AF: 0.677 AC: 3486 AN: 5148

South Asian (SAS) AF: 0.682 AC: 3281 AN: 4812

European-Finnish (FIN) AF: 0.603 AC: 6365 AN: 10556

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.577 AC: 39200 AN: 67954

Other (OTH) AF: 0.632 AC: 1336 AN: 2114

Alfa AF: 0.598 Hom.: 13934

Bravo AF: 0.661

Asia WGS AF: 0.691 AC: 2404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.70
DANN	Benign	0.48
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs2040273; hg19: chr21-27232198;