21-46021401-C-T

Variant names:

• chr21-46021401-C-T
• rs2839081

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 0.43 in 148,084 control chromosomes in the GnomAD database, including 14,793 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 0.43 (14793 hom., cov: 26)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892
• Publications: 12 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 (EAS) allele frequency at 95% confidence interval = 0.679 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: 0.430 AC: 63595 AN: 148000 Hom.: 14788 Cov.: 26

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.430 AC: 63620 AN: 148084 Hom.: 14793 Cov.: 26 AF XY: 0.435 AC XY: 31267 AN XY: 71910

African (AFR) AF: 0.234 AC: 9382 AN: 40056

American (AMR) AF: 0.546 AC: 8131 AN: 14892

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1812 AN: 3448

East Asian (EAS) AF: 0.698 AC: 3513 AN: 5032

South Asian (SAS) AF: 0.530 AC: 2437 AN: 4600

European-Finnish (FIN) AF: 0.505 AC: 4882 AN: 9672

Middle Eastern (MID) AF: 0.486 AC: 136 AN: 280

European-Non Finnish (NFE) AF: 0.474 AC: 31820 AN: 67132

Other (OTH) AF: 0.465 AC: 962 AN: 2070

Alfa AF: 0.464 Hom.: 9541

Bravo AF: 0.423

Asia WGS AF: 0.595 AC: 2069 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.50
PhyloP100		-0.89

Splicing

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

Other links and lift over

dbSNP: rs2839081; hg19: chr21-47441315;