rs1980653

Positions:

• chr10-103894406-A-G
• chr10-103894406-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024928.5(STN1):​c.754-2154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,910 control chromosomes in the GnomAD database, including 15,720 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 (15720 hom., cov: 31)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331

Genes affected

STN1 (HGNC:26200): (STN1 subunit of CST complex) OBFC1 and C17ORF68 (MIM 613129) are subunits of an alpha accessory factor (AAF) that stimulates the activity of DNA polymerase-alpha-primase (see MIM 176636), the enzyme that initiates DNA replication (Casteel et al., 2009 [PubMed 19119139]). OBFC1 also appears to function in a telomere-associated complex with C17ORF68 and TEN1 (C17ORF106; MIM 613130) (Miyake et al., 2009 [PubMed 19854130]).[supplied by OMIM, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STN1	NM_024928.5	c.754-2154T>C		intron_variant		ENST00000224950.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STN1	ENST00000224950.8	c.754-2154T>C		intron_variant		1	NM_024928.5	P1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67546 AN: 151792 Hom.: 15714 Cov.: 31

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.445 AC: 67562 AN: 151910 Hom.: 15720 Cov.: 31 AF XY: 0.449 AC XY: 33301 AN XY: 74222

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.458

Alfa AF: 0.480 Hom.: 8138

Bravo AF: 0.433

Asia WGS AF: 0.366 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1980653; hg19: chr10-105654164;