21-21848768-A-G

Variant names:

• chr21-21848768-A-G
• rs2827093

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 0.192 in 152,136 control chromosomes in the GnomAD database, including 3,588 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 (3588 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 2 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• 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: 0.192 AC: 29251 AN: 152016 Hom.: 3586 Cov.: 32

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.0435

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.192 AC: 29250 AN: 152136 Hom.: 3588 Cov.: 32 AF XY: 0.190 AC XY: 14096 AN XY: 74344

African (AFR) AF: 0.0509 AC: 2113 AN: 41542

American (AMR) AF: 0.239 AC: 3644 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1247 AN: 3470

East Asian (EAS) AF: 0.0436 AC: 225 AN: 5162

South Asian (SAS) AF: 0.185 AC: 895 AN: 4830

European-Finnish (FIN) AF: 0.223 AC: 2355 AN: 10572

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17858 AN: 67978

Other (OTH) AF: 0.225 AC: 474 AN: 2110

Alfa AF: 0.238 Hom.: 3390

Bravo AF: 0.187

Asia WGS AF: 0.137 AC: 481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.63
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs2827093; hg19: chr21-23221088;