rs1637001

Positions:

• chr7-100210528-G-A

Variant summary

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

The NM_001282717.2(STAG3):​c.3239-483G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 151,836 control chromosomes in the GnomAD database, including 38,597 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 0.71 (38597 hom., cov: 30)
• Consequence: STAG3 NM_001282717.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

Genes affected

STAG3 (HGNC:11356): (STAG3 cohesin complex component) The protein encoded by this gene is expressed in the nucleus and is a subunit of the cohesin complex which regulates the cohesion of sister chromatids during cell division. A mutation in this gene is associated with premature ovarian failure. Alternate splicing results in multiple transcript variants encoding distinct isoforms. This gene has multiple pseudogenes. [provided by RefSeq, Apr 2014]

CASTOR3P (HGNC:29954): (CASTOR family member 3, pseudogene) Predicted to be involved in cellular response to L-arginine and negative regulation of TORC1 signaling. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAG3	NM_001282717.2	c.3239-483G>A		intron_variant		ENST00000615138.5
CASTOR3P	NR_028040.1	n.914-7925C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAG3	ENST00000615138.5	c.3239-483G>A		intron_variant		1	NM_001282717.2	A2
CASTOR3P	ENST00000649671.1	n.776-7925C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107271 AN: 151718 Hom.: 38570 Cov.: 30

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.707 AC: 107339 AN: 151836 Hom.: 38597 Cov.: 30 AF XY: 0.702 AC XY: 52130 AN XY: 74220

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.723

Alfa AF: 0.731 Hom.: 65057

Bravo AF: 0.693

Asia WGS AF: 0.574 AC: 1992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.40

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: rs1637001; hg19: chr7-99808151;