Genetic Variant STAG1:c.3672+4_3672+11delGAGAAATT (chr3-136340479-GAATTTCTC-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_005862.3(STAG1):c.3672+4_3672+11delGAGAAATT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000264 in 1,548,324 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 1 hom. )

Consequence

STAG1
NM_005862.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.40

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 3-136340479-GAATTTCTC-G is Benign according to our data. Variant chr3-136340479-GAATTTCTC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1695084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000407 (62/152244) while in subpopulation NFE AF = 0.000147 (10/68016). AF 95% confidence interval is 0.0000791. There are 0 homozygotes in GnomAd4. There are 40 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG1	NM_005862.3 link	c.3672+4_3672+11delGAGAAATT		splice_region_variant, intron_variant	Intron 32 of 33	ENST00000383202.7	NP_005853.2	Q8WVM7-1Q4LE48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG1	ENST00000383202.7 link	c.3672+4_3672+11delGAGAAATT		splice_region_variant, intron_variant	Intron 32 of 33	1	NM_005862.3	ENSP00000372689.2		Q8WVM7-1

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000406

AC:

102

AN:

251072

AF XY:

0.000420

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00388

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000248

AC:

346

AN:

1396080

Hom.:

AF XY:

0.000249

AC XY:

174

AN XY:

698756

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

AC:

AN:

32202

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

44632

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25748

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39332

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

84980

Gnomad4 FIN exome

AF:

0.00390

AC:

208

AN:

53364

Gnomad4 NFE exome

AF:

0.000127

AC:

134

AN:

1052050

Gnomad4 Remaining exome

AF:

0.0000516

AC:

AN:

58140

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000407

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000482

AC:

0.0000481603

AN:

0.0000481603

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00472

AC:

0.00471698

AN:

0.00471698

Gnomad4 NFE

AF:

0.000147

AC:

0.000147024

AN:

0.000147024

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.000291

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

STAG1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=8/92

disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over