Genetic Variant STAG1:c.3558-14C>T (chr3-136340619-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005862.3(STAG1):c.3558-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,556,720 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 46 hom. )

Consequence

STAG1
NM_005862.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.163

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 3-136340619-G-A is Benign according to our data. Variant chr3-136340619-G-A is described in ClinVar as [Benign]. Clinvar id is 1971461.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00332 (505/152240) while in subpopulation EAS AF = 0.0463 (240/5180). AF 95% confidence interval is 0.0415. There are 7 homozygotes in GnomAd4. There are 262 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 505 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG1	NM_005862.3 link	c.3558-14C>T		intron_variant	Intron 31 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.3558-14C>T		intron_variant	Intron 31 of 33	1	NM_005862.3	ENSP00000372689.2		Q8WVM7-1

Frequencies

GnomAD3 genomes

AF:

0.00328

AC:

499

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00519

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0464

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00436

AC:

1095

AN:

250996

AF XY:

0.00367

show subpopulations

Gnomad AFR exome

AF:

0.00652

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0497

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00160

AC:

2249

AN:

1404480

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

1072

AN XY:

702538

show subpopulations

Gnomad4 AFR exome

AF:

0.00784

AC:

254

AN:

32382

Gnomad4 AMR exome

AF:

0.000672

AC:

AN:

44654

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25794

Gnomad4 EAS exome

AF:

0.0390

AC:

1537

AN:

39412

Gnomad4 SAS exome

AF:

0.00119

AC:

101

AN:

85056

Gnomad4 FIN exome

AF:

0.000112

AC:

AN:

53376

Gnomad4 NFE exome

AF:

0.0000642

AC:

AN:

1059742

Gnomad4 Remaining exome

AF:

0.00409

AC:

239

AN:

58408

Heterozygous variant carriers

106

213

319

426

532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.00332

AC:

505

AN:

152240

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00520

AC:

0.00519756

AN:

0.00519756

Gnomad4 AMR

AF:

0.00111

AC:

0.00111184

AN:

0.00111184

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.0463

AC:

0.046332

AN:

0.046332

Gnomad4 SAS

AF:

0.00229

AC:

0.00228595

AN:

0.00228595

Gnomad4 FIN

AF:

0.0000943

AC:

0.0000942685

AN:

0.0000942685

Gnomad4 NFE

AF:

0.0000588

AC:

0.0000588166

AN:

0.0000588166

Gnomad4 OTH

AF:

0.00758

AC:

0.00757576

AN:

0.00757576

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

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:

0.00153

Hom.:

Bravo

AF:

0.00342

Asia WGS

AF:

0.0350

AC:

121

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.1

DANN

Benign

0.80

Mutation Taster

=100/0

polymorphism

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

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