3-136340475-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005862.3(STAG1):c.3672+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,517,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: STAG1 NM_005862.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.691

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-136340475-T-C is Benign according to our data. Variant chr3-136340475-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1971187.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000184 (28/152286) while in subpopulation NFE AF= 0.000294 (20/68016). AF 95% confidence interval is 0.000194. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAG1	NM_005862.3	c.3672+16A>G		intron_variant		ENST00000383202.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAG1	ENST00000383202.7	c.3672+16A>G		intron_variant		1	NM_005862.3	P1

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000183 AC: 46 AN: 251010 Hom.: 0 AF XY: 0.000206 AC XY: 28 AN XY: 135672

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000244 AC: 333 AN: 1365656 Hom.: 0 Cov.: 21 AF XY: 0.000266 AC XY: 182 AN XY: 685226

Gnomad4 AFR exome AF: 0.0000316

Gnomad4 AMR exome AF: 0.000247

Gnomad4 ASJ exome AF: 0.000195

Gnomad4 EAS exome AF: 0.000128

Gnomad4 SAS exome AF: 0.0000356

Gnomad4 FIN exome AF: 0.0000937

Gnomad4 NFE exome AF: 0.000278

Gnomad4 OTH exome AF: 0.000245

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74468

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000144 Hom.: 0

Bravo AF: 0.000140

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 27, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.21
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs374980869; hg19: chr3-136059317;