chr10-103894633-T-G

Variant names:

• chr10-103894633-T-G
• rs4918069
• NM_024928.5:c.754-2381A>C

Variant summary

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

The NM_024928.5(STN1):​c.754-2381A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,060 control chromosomes in the GnomAD database, including 4,207 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 (4207 hom., cov: 29)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024928.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STN1	NM_024928.5	MANE Select	c.754-2381A>C		intron	N/A	NP_079204.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STN1	ENST00000224950.8	TSL:1 MANE Select	c.754-2381A>C		intron	N/A	ENSP00000224950.3
	STN1	ENST00000698305.1		c.754-2381A>C		intron	N/A	ENSP00000513665.1
	STN1	ENST00000369764.2	TSL:2	c.754-2381A>C		intron	N/A	ENSP00000358779.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33743 AN: 150950 Hom.: 4208 Cov.: 29

Gnomad AFR AF: 0.0978

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.223 AC: 33744 AN: 151060 Hom.: 4207 Cov.: 29 AF XY: 0.227 AC XY: 16700 AN XY: 73676

African (AFR) AF: 0.0976 AC: 4027 AN: 41254

American (AMR) AF: 0.264 AC: 4012 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 588 AN: 3466

East Asian (EAS) AF: 0.184 AC: 945 AN: 5136

South Asian (SAS) AF: 0.267 AC: 1273 AN: 4776

European-Finnish (FIN) AF: 0.359 AC: 3654 AN: 10182

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18355 AN: 67770

Other (OTH) AF: 0.225 AC: 474 AN: 2106

Alfa AF: 0.250 Hom.: 7843

Bravo AF: 0.211

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	14
DANN	Benign	0.55
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4918069; hg19: chr10-105654391;