3-136672353-A-G

Variant names:

• chr3-136672353-A-G
• rs3856637
• NM_005862.3:c.-83-41372T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005862.3(STAG1):​c.-83-41372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,230 control chromosomes in the GnomAD database, including 6,361 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 0.29 (6361 hom., cov: 32)
• Consequence: STAG1 NM_005862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG1	NM_005862.3	c.-83-41372T>C		intron_variant	Intron 1 of 33	ENST00000383202.7	NP_005853.2
STAG1	XR_001739978.2	n.185-41372T>C		intron_variant	Intron 1 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG1	ENST00000383202.7	c.-83-41372T>C		intron_variant	Intron 1 of 33	1	NM_005862.3	ENSP00000372689.2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43773 AN: 152112 Hom.: 6355 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.288 AC: 43801 AN: 152230 Hom.: 6361 Cov.: 32 AF XY: 0.287 AC XY: 21330 AN XY: 74442

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.304

Alfa AF: 0.264 Hom.: 2805

Bravo AF: 0.289

Asia WGS AF: 0.177 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.73

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: rs3856637; hg19: chr3-136391195;