rs2902638

Variant names:

• chr10-103877231-T-C
• rs2902638
• ENST00000698241.1:c.*39+5414A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000698241.1(STN1):​c.*39+5414A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,246 control chromosomes in the GnomAD database, including 3,820 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 (3820 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: STN1 ENST00000698241.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 5 publications found

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]

STN1 Gene-Disease associations (from GenCC):

• cerebroretinal microangiopathy with calcifications and cysts 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Ambry Genetics, Genomics England PanelApp
• Coats plus syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289744 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 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
STN1	ENST00000698241.1	c.*39+5414A>G		intron_variant	Intron 10 of 10			ENSP00000513621.1
STN1	ENST00000698242.1	c.*39+5414A>G		intron_variant	Intron 10 of 10			ENSP00000513622.1
STN1	ENST00000698297.1	c.*39+5414A>G		intron_variant	Intron 10 of 10			ENSP00000513657.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32808 AN: 152128 Hom.: 3818 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.216 AC: 32816 AN: 152246 Hom.: 3820 Cov.: 33 AF XY: 0.218 AC XY: 16242 AN XY: 74426

African (AFR) AF: 0.118 AC: 4889 AN: 41560

American (AMR) AF: 0.257 AC: 3924 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3472

East Asian (EAS) AF: 0.168 AC: 871 AN: 5188

South Asian (SAS) AF: 0.256 AC: 1233 AN: 4822

European-Finnish (FIN) AF: 0.317 AC: 3356 AN: 10584

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17113 AN: 68008

Other (OTH) AF: 0.218 AC: 461 AN: 2112

Alfa AF: 0.236 Hom.: 13569

Bravo AF: 0.206

Asia WGS AF: 0.205 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	17
DANN	Benign	0.83
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs2902638; hg19: chr10-105636989;