chr3-136683218-G-A

Position:

• chr3-136683218-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2023 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAG1	NM_005862.3	c.-83-52237C>T		intron_variant		ENST00000383202.7	NP_005853.2
STAG1	XR_001739978.2	n.185-52237C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAG1	ENST00000383202.7	c.-83-52237C>T		intron_variant		1	NM_005862.3	ENSP00000372689.2

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2023 AN: 151936 Hom.: 28 Cov.: 32

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.: 28 Cov.: 32 AF XY: 0.0129 AC XY: 957 AN XY: 74316

Gnomad4 AFR AF: 0.00427

Gnomad4 AMR AF: 0.0294

Gnomad4 ASJ AF: 0.0332

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00180

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0137 Hom.: 1

Bravo AF: 0.0144

Asia WGS AF: 0.00347 AC: 12 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
DANN	Benign	0.60

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: rs9826828; hg19: chr3-136402060;