21-45005762-T-A

Position:

• chr21-45005762-T-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The variant allele was found at a frequency of 0.00215 in 152,286 control chromosomes in the GnomAD database, including 1 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 0.0022 (1 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00215 (328/152286) while in subpopulation EAS AF= 0.0389 (202/5190). AF 95% confidence interval is 0.0345. There are 1 homozygotes in gnomad4. There are 193 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 329 AN: 152168 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0388

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00191

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

GnomAD4 genome AF: 0.00215 AC: 328 AN: 152286 Hom.: 1 Cov.: 32 AF XY: 0.00259 AC XY: 193 AN XY: 74470

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.0389

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00472

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000953 Hom.: 0

Bravo AF: 0.00213

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.69
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs36221779; hg19: chr21-46425677;