rs4522658

Variant names:

• chr2-133729592-G-A
• rs4522658

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 0.435 in 151,986 control chromosomes in the GnomAD database, including 15,100 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 0.44 (15100 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 6 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 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: 0.435 AC: 66099 AN: 151866 Hom.: 15079 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.435 AC: 66161 AN: 151986 Hom.: 15100 Cov.: 32 AF XY: 0.435 AC XY: 32281 AN XY: 74274

African (AFR) AF: 0.346 AC: 14338 AN: 41452

American (AMR) AF: 0.440 AC: 6732 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1246 AN: 3464

East Asian (EAS) AF: 0.263 AC: 1354 AN: 5158

South Asian (SAS) AF: 0.334 AC: 1610 AN: 4814

European-Finnish (FIN) AF: 0.588 AC: 6200 AN: 10550

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33315 AN: 67956

Other (OTH) AF: 0.408 AC: 860 AN: 2108

Alfa AF: 0.462 Hom.: 27830

Bravo AF: 0.424

Asia WGS AF: 0.355 AC: 1233 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.37
PhyloP100		-0.065

Splicing

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

Other links and lift over

dbSNP: rs4522658; hg19: chr2-134487163;