3-136390670-A-G

Variant names:

• chr3-136390670-A-G
• rs698270
• NM_005862.3:c.2277+8079T>C

Variant summary

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

The NM_005862.3(STAG1):​c.2277+8079T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,178 control chromosomes in the GnomAD database, including 45,557 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 0.77 (45557 hom., cov: 32)
• Consequence: STAG1 NM_005862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539
• Publications: 5 publications found

Genes affected

STAG1 (HGNC:11354): (STAG1 cohesin complex component) This gene is a member of the SCC3 family and is expressed in the nucleus. It encodes a component of cohesin, a multisubunit protein complex that provides sister chromatid cohesion along the length of a chromosome from DNA replication through prophase and prometaphase, after which it is dissociated in preparation for segregation during anaphase. [provided by RefSeq, Jul 2008]

STAG1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 47

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG1	NM_005862.3	c.2277+8079T>C		intron_variant	Intron 22 of 33	ENST00000383202.7	NP_005853.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG1	ENST00000383202.7	c.2277+8079T>C		intron_variant	Intron 22 of 33	1	NM_005862.3	ENSP00000372689.2

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117552 AN: 152060 Hom.: 45519 Cov.: 32

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.773 AC: 117644 AN: 152178 Hom.: 45557 Cov.: 32 AF XY: 0.778 AC XY: 57874 AN XY: 74408

African (AFR) AF: 0.737 AC: 30587 AN: 41516

American (AMR) AF: 0.766 AC: 11707 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2447 AN: 3468

East Asian (EAS) AF: 0.859 AC: 4453 AN: 5184

South Asian (SAS) AF: 0.823 AC: 3969 AN: 4824

European-Finnish (FIN) AF: 0.869 AC: 9205 AN: 10592

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52884 AN: 68002

Other (OTH) AF: 0.743 AC: 1573 AN: 2116

Alfa AF: 0.775 Hom.: 23027

Bravo AF: 0.763

Asia WGS AF: 0.834 AC: 2899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.62
PhyloP100		0.54
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: rs698270; hg19: chr3-136109512;