rs457581

Variant names:

• chr21-26222161-G-A
• rs457581

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 0.187 in 152,172 control chromosomes in the GnomAD database, including 3,247 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 0.19 (3247 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549
• Publications: 17 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 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: 0.187 AC: 28449 AN: 152054 Hom.: 3247 Cov.: 32

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.187 AC: 28444 AN: 152172 Hom.: 3247 Cov.: 32 AF XY: 0.183 AC XY: 13588 AN XY: 74378

African (AFR) AF: 0.0642 AC: 2669 AN: 41544

American (AMR) AF: 0.182 AC: 2783 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3470

East Asian (EAS) AF: 0.168 AC: 869 AN: 5170

South Asian (SAS) AF: 0.119 AC: 572 AN: 4820

European-Finnish (FIN) AF: 0.236 AC: 2497 AN: 10566

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17848 AN: 67994

Other (OTH) AF: 0.173 AC: 365 AN: 2114

Alfa AF: 0.237 Hom.: 14464

Bravo AF: 0.179

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.61
PhyloP100		0.55

Splicing

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

Other links and lift over

dbSNP: rs457581; hg19: chr21-27594480;