21-23249105-T-C

Variant names:

• chr21-23249105-T-C
• rs2827991

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.355 in 151,592 control chromosomes in the GnomAD database, including 11,650 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 0.36 (11650 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.956

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 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: 0.355 AC: 53836 AN: 151474 Hom.: 11652 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.355 AC: 53817 AN: 151592 Hom.: 11650 Cov.: 32 AF XY: 0.357 AC XY: 26407 AN XY: 74060

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.353

Alfa AF: 0.404 Hom.: 1697

Bravo AF: 0.341

Asia WGS AF: 0.291 AC: 1010 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.012
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2827991; hg19: chr21-24621427;