rs225359

Variant names:

• chr21-42367327-G-A
• rs225359

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 0.616 in 151,898 control chromosomes in the GnomAD database, including 29,888 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 0.62 (29888 hom., cov: 30)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561
• Publications: 6 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 = 0.692 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: 0.616 AC: 93454 AN: 151780 Hom.: 29871 Cov.: 30

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.616 AC: 93515 AN: 151898 Hom.: 29888 Cov.: 30 AF XY: 0.614 AC XY: 45594 AN XY: 74228

African (AFR) AF: 0.477 AC: 19722 AN: 41362

American (AMR) AF: 0.661 AC: 10102 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2473 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1346 AN: 5170

South Asian (SAS) AF: 0.564 AC: 2717 AN: 4816

European-Finnish (FIN) AF: 0.730 AC: 7700 AN: 10548

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47341 AN: 67944

Other (OTH) AF: 0.610 AC: 1285 AN: 2106

Alfa AF: 0.675 Hom.: 106525

Bravo AF: 0.605

Asia WGS AF: 0.458 AC: 1594 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	2.0
DANN	Benign	0.84
PhyloP100		-0.56

Splicing

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

Other links and lift over

dbSNP: rs225359; hg19: chr21-43787436;