21-23641815-T-C

Variant names:

• chr21-23641815-T-C
• rs169476

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 0.157 in 151,998 control chromosomes in the GnomAD database, including 1,884 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 0.16 (1884 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• Publications: 3 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 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: 0.157 AC: 23805 AN: 151882 Hom.: 1886 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.157 AC: 23808 AN: 151998 Hom.: 1884 Cov.: 32 AF XY: 0.153 AC XY: 11354 AN XY: 74312

African (AFR) AF: 0.166 AC: 6895 AN: 41494

American (AMR) AF: 0.108 AC: 1644 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3464

East Asian (EAS) AF: 0.103 AC: 532 AN: 5176

South Asian (SAS) AF: 0.196 AC: 947 AN: 4826

European-Finnish (FIN) AF: 0.129 AC: 1362 AN: 10592

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11508 AN: 67878

Other (OTH) AF: 0.159 AC: 334 AN: 2106

Alfa AF: 0.164 Hom.: 6614

Bravo AF: 0.153

Asia WGS AF: 0.146 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.52
PhyloP100		-0.48

Splicing

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

Other links and lift over

dbSNP: rs169476; hg19: chr21-25014133;