22-46145351-A-G

Variant names:

• chr22-46145351-A-G
• rs135557

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 0.504 in 151,772 control chromosomes in the GnomAD database, including 21,415 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 0.50 (21415 hom., cov: 30)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 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: 0.504 AC: 76413 AN: 151654 Hom.: 21367 Cov.: 30

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.504 AC: 76514 AN: 151772 Hom.: 21415 Cov.: 30 AF XY: 0.494 AC XY: 36624 AN XY: 74158

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.453

Alfa AF: 0.444 Hom.: 20641

Bravo AF: 0.513

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs135557; hg19: chr22-46541227;