rs12999653

Positions:

• chr2-216612454-C-A

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 0.142 in 152,166 control chromosomes in the GnomAD database, including 1,829 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 0.14 (1829 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

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: 0.142 AC: 21620 AN: 152048 Hom.: 1816 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0920

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.142 AC: 21662 AN: 152166 Hom.: 1829 Cov.: 32 AF XY: 0.144 AC XY: 10705 AN XY: 74408

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.0631

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.0919

Gnomad4 OTH AF: 0.130

Alfa AF: 0.108 Hom.: 568

Bravo AF: 0.153

Asia WGS AF: 0.215 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12999653; hg19: chr2-217477177;