rs3814219

Positions:

• chr10-103887337-G-A
• chr10-103887337-G-C

Variant summary

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

The NM_024928.5(STN1):​c.949+1735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,118 control chromosomes in the GnomAD database, including 3,756 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 0.22 (3756 hom., cov: 32)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STN1	NM_024928.5	c.949+1735C>T		intron_variant		ENST00000224950.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STN1	ENST00000224950.8	c.949+1735C>T		intron_variant		1	NM_024928.5	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33226 AN: 151998 Hom.: 3751 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.218 AC: 33237 AN: 152118 Hom.: 3756 Cov.: 32 AF XY: 0.218 AC XY: 16202 AN XY: 74360

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.228

Alfa AF: 0.226 Hom.: 7023

Bravo AF: 0.221

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.66

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: rs3814219; hg19: chr10-105647095;