rs12828230

Variant names:

• chr12-55491234-C-T
• rs12828230
• ENST00000554049.1:n.89+1857G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000554049.1(ENSG00000258763):​n.89+1857G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 151,986 control chromosomes in the GnomAD database, including 116 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 0.030 (116 hom., cov: 32)
• Consequence: ENSG00000258763 ENST00000554049.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.386
• Publications: 2 publications found

Genes affected

ENSG00000258763 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0302 (4590/151986) while in subpopulation NFE AF = 0.0441 (2996/67936). AF 95% confidence interval is 0.0428. There are 116 homozygotes in GnomAd4. There are 2296 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 116 gene

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
ENSG00000258763	ENST00000554049.1	n.89+1857G>A		intron_variant	Intron 1 of 2	2
ENSG00000258763	ENST00000555138.2	n.210+1857G>A		intron_variant	Intron 3 of 3	2
ENSG00000258763	ENST00000556750.6	n.210+1857G>A		intron_variant	Intron 3 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4594 AN: 151868 Hom.: 116 Cov.: 32

Gnomad AFR AF: 0.00723

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0125

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.0230

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

GnomAD4 genome AF: 0.0302 AC: 4590 AN: 151986 Hom.: 116 Cov.: 32 AF XY: 0.0309 AC XY: 2296 AN XY: 74288

African (AFR) AF: 0.00721 AC: 299 AN: 41470

American (AMR) AF: 0.0184 AC: 281 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0259 AC: 90 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0125 AC: 60 AN: 4810

European-Finnish (FIN) AF: 0.0763 AC: 806 AN: 10560

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0441 AC: 2996 AN: 67936

Other (OTH) AF: 0.0228 AC: 48 AN: 2108

Alfa AF: 0.0361 Hom.: 13

Bravo AF: 0.0249

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.71
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs12828230; hg19: chr12-55885018;