3-136553404-T-C

Variant names:

• chr3-136553404-T-C
• rs7621025
• NM_005862.3:c.395-11209A>G

Variant summary

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

The NM_005862.3(STAG1):​c.395-11209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,132 control chromosomes in the GnomAD database, including 42,986 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 0.75 (42986 hom., cov: 33)
• Consequence: STAG1 NM_005862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 15 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, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005862.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG1	NM_005862.3	MANE Select	c.395-11209A>G		intron	N/A	NP_005853.2	Q8WVM7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG1	ENST00000383202.7	TSL:1 MANE Select	c.395-11209A>G		intron	N/A	ENSP00000372689.2	Q8WVM7-1
	STAG1	ENST00000236698.9	TSL:1	c.395-11209A>G		intron	N/A	ENSP00000236698.5	Q8WVM7-2
	STAG1	ENST00000483235.5	TSL:1	n.*319-11209A>G		intron	N/A	ENSP00000419093.1	F8WF82

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114130 AN: 152014 Hom.: 42945 Cov.: 33

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.751 AC: 114226 AN: 152132 Hom.: 42986 Cov.: 33 AF XY: 0.757 AC XY: 56281 AN XY: 74382

African (AFR) AF: 0.712 AC: 29543 AN: 41486

American (AMR) AF: 0.757 AC: 11564 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2388 AN: 3470

East Asian (EAS) AF: 0.861 AC: 4462 AN: 5182

South Asian (SAS) AF: 0.806 AC: 3891 AN: 4826

European-Finnish (FIN) AF: 0.861 AC: 9109 AN: 10576

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 50965 AN: 67998

Other (OTH) AF: 0.720 AC: 1522 AN: 2114

Alfa AF: 0.744 Hom.: 31663

Bravo AF: 0.741

Asia WGS AF: 0.834 AC: 2898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.52
PhyloP100		-1.1
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: rs7621025; hg19: chr3-136272246;