21-39145849-A-G

Variant names:

• chr21-39145849-A-G
• rs8126528

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 0.892 in 152,200 control chromosomes in the GnomAD database, including 60,692 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 0.89 (60692 hom., cov: 31)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 3 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 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: 0.892 AC: 135650 AN: 152082 Hom.: 60642 Cov.: 31

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.898

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.892 AC: 135757 AN: 152200 Hom.: 60692 Cov.: 31 AF XY: 0.893 AC XY: 66429 AN XY: 74412

African (AFR) AF: 0.965 AC: 40081 AN: 41540

American (AMR) AF: 0.884 AC: 13513 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 2991 AN: 3472

East Asian (EAS) AF: 0.858 AC: 4455 AN: 5192

South Asian (SAS) AF: 0.878 AC: 4236 AN: 4826

European-Finnish (FIN) AF: 0.855 AC: 9044 AN: 10580

Middle Eastern (MID) AF: 0.894 AC: 261 AN: 292

European-Non Finnish (NFE) AF: 0.859 AC: 58376 AN: 67990

Other (OTH) AF: 0.901 AC: 1905 AN: 2114

Alfa AF: 0.869 Hom.: 21078

Bravo AF: 0.896

Asia WGS AF: 0.881 AC: 3066 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	2.4
DANN	Benign	0.34
PhyloP100		-0.57

Splicing

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

Other links and lift over

dbSNP: rs8126528; hg19: chr21-40517775;