dbSNP rs9826828: STAG1:c.-83-52237C>T (chr3-136683218-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005862.3(STAG1):c.-83-52237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 152,050 control chromosomes in the GnomAD database, including 28 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 0.013 ( 28 hom., cov: 32)

Consequence

STAG1
NM_005862.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.265

Publications

24 publications found

Variant links:

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

STAG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0133 (2023/152050) while in subpopulation AMR AF = 0.0294 (448/15256). AF 95% confidence interval is 0.0271. There are 28 homozygotes in GnomAd4. There are 957 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2023 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG1	NM_005862.3 link	c.-83-52237C>T		intron_variant	Intron 1 of 33	ENST00000383202.7	NP_005853.2	Q8WVM7-1Q4LE48
STAG1	XR_001739978.2 link	n.185-52237C>T		intron_variant	Intron 1 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG1	ENST00000383202.7 link	c.-83-52237C>T		intron_variant	Intron 1 of 33	1	NM_005862.3	ENSP00000372689.2		Q8WVM7-1

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2023

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00428

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0294

Gnomad ASJ

AF:

0.0332

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00180

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0174

Gnomad OTH

AF:

0.0273

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

GnomAD4 genome

AF:

0.0133

AC:

2023

AN:

152050

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

957

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.00427

AC:

177

AN:

41486

American (AMR)

AF:

0.0294

AC:

448

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0332

AC:

115

AN:

3466

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.00228

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00180

AC:

AN:

10534

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0174

AC:

1186

AN:

67990

Other (OTH)

AF:

0.0265

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

105

209

314

418

523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00442

Hom.:

Bravo

AF:

0.0144

Asia WGS

AF:

0.00347

AC:

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.7

(source)

DANN

Benign

0.60

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over