rs12456774

Variant names:

• chr18-22592612-G-A
• rs12456774

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 0.176 in 152,156 control chromosomes in the GnomAD database, including 2,595 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 0.18 (2595 hom., cov: 33)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932
• Publications: 3 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 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: 0.176 AC: 26717 AN: 152038 Hom.: 2600 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.0987

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.176 AC: 26709 AN: 152156 Hom.: 2595 Cov.: 33 AF XY: 0.176 AC XY: 13064 AN XY: 74382

African (AFR) AF: 0.228 AC: 9469 AN: 41498

American (AMR) AF: 0.186 AC: 2838 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3468

East Asian (EAS) AF: 0.309 AC: 1600 AN: 5176

South Asian (SAS) AF: 0.220 AC: 1063 AN: 4822

European-Finnish (FIN) AF: 0.0987 AC: 1046 AN: 10596

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9771 AN: 67992

Other (OTH) AF: 0.164 AC: 345 AN: 2110

Alfa AF: 0.173 Hom.: 355

Bravo AF: 0.184

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.64
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs12456774; hg19: chr18-20172575;