3-136553404-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAG1	NM_005862.3	c.395-11209A>G		intron_variant		ENST00000383202.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAG1	ENST00000383202.7	c.395-11209A>G		intron_variant		1	NM_005862.3	P1

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

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.720

Alfa AF: 0.745 Hom.: 26378

Bravo AF: 0.741

Asia WGS AF: 0.834 AC: 2898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.10
Dann	Benign	0.52

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: rs7621025; hg19: chr3-136272246;