rs17221259

Variant names:

• chr12-14257551-T-C
• rs17221259
• ENST00000774772.1:n.-122T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000774772.1(ENSG00000300868):​n.-122T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,040 control chromosomes in the GnomAD database, including 2,022 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 0.15 (2022 hom., cov: 32)
• Consequence: ENSG00000300868 ENST00000774772.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 17 publications found

Genes affected

ENSG00000300868 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 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
ENSG00000300868	ENST00000774772.1	n.-122T>C		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22118 AN: 151924 Hom.: 2023 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.145 AC: 22110 AN: 152040 Hom.: 2022 Cov.: 32 AF XY: 0.146 AC XY: 10850 AN XY: 74312

African (AFR) AF: 0.0348 AC: 1443 AN: 41474

American (AMR) AF: 0.127 AC: 1933 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3468

East Asian (EAS) AF: 0.227 AC: 1172 AN: 5166

South Asian (SAS) AF: 0.198 AC: 952 AN: 4814

European-Finnish (FIN) AF: 0.195 AC: 2052 AN: 10550

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13258 AN: 67970

Other (OTH) AF: 0.159 AC: 336 AN: 2112

Alfa AF: 0.178 Hom.: 7231

Bravo AF: 0.136

Asia WGS AF: 0.190 AC: 659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		2.0

Splicing

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

Other links and lift over

dbSNP: rs17221259; hg19: chr12-14410485;