chr21-42315531-G-C

Position:

• chr21-42315531-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The variant allele was found at a frequency of 0.00193 in 1,539,168 control chromosomes in the GnomAD database, including 43 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 0.0080 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (30 hom.)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00798 (1215/152320) while in subpopulation AFR AF= 0.0247 (1026/41570). AF 95% confidence interval is 0.0234. There are 13 homozygotes in gnomad4. There are 586 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00796 AC: 1211 AN: 152202 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00287 AC: 720 AN: 250884 Hom.: 10 AF XY: 0.00260 AC XY: 353 AN XY: 135580

Gnomad AFR exome AF: 0.0274

Gnomad AMR exome AF: 0.00324

Gnomad ASJ exome AF: 0.00559

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000309

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00126 AC: 1750 AN: 1386848 Hom.: 30 Cov.: 21 AF XY: 0.00128 AC XY: 890 AN XY: 694126

Gnomad4 AFR exome AF: 0.0296

Gnomad4 AMR exome AF: 0.00328

Gnomad4 ASJ exome AF: 0.00571

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00245

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000137

Gnomad4 OTH exome AF: 0.00236

GnomAD4 genome AF: 0.00798 AC: 1215 AN: 152320 Hom.: 13 Cov.: 33 AF XY: 0.00787 AC XY: 586 AN XY: 74480

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.00713

Gnomad4 ASJ AF: 0.00779

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.00322 Hom.: 3

Bravo AF: 0.00900

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs77436142; hg19: chr21-43735641;