1-167114567-A-G

Position:

• chr1-167114567-A-G

Variant summary

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

The NM_001080426.3(STYXL2):​c.205+763A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,716 control chromosomes in the GnomAD database, including 16,808 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 0.47 (16808 hom., cov: 30)
• Consequence: STYXL2 NM_001080426.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

Genes affected

STYXL2 (HGNC:25034): (serine/threonine/tyrosine interacting like 2) Predicted to enable protein tyrosine/serine/threonine phosphatase activity. Predicted to be involved in protein dephosphorylation. Predicted to be located in sarcomere. [provided by Alliance of Genome Resources, Apr 2022]

GPA33 (HGNC:4445): (glycoprotein A33) The glycoprotein encoded by this gene is a cell surface antigen that is expressed in greater than 95% of human colon cancers. The open reading frame encodes a 319-amino acid polypeptide having a putative secretory signal sequence and 3 potential glycosylation sites. The predicted mature protein has a 213-amino acid extracellular region, a single transmembrane domain, and a 62-amino acid intracellular tail. The sequence of the extracellular region contains 2 domains characteristic of the CD2 subgroup of the immunoglobulin (Ig) superfamily. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STYXL2	NM_001080426.3	c.205+763A>G		intron_variant		ENST00000361200.7	NP_001073895.1
STYXL2	XM_011510146.3	c.88+763A>G		intron_variant			XP_011508448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STYXL2	ENST00000361200.7	c.205+763A>G		intron_variant		5	NM_001080426.3	ENSP00000354483	P1
STYXL2	ENST00000271385.9	c.205+763A>G		intron_variant		1		ENSP00000271385	P1
STYXL2	ENST00000443333.1	c.205+763A>G		intron_variant		5		ENSP00000404874	P1
GPA33	ENST00000632571.1	c.-281-41028T>C		intron_variant		4		ENSP00000488407

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70803 AN: 151598 Hom.: 16805 Cov.: 30

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.467 AC: 70838 AN: 151716 Hom.: 16808 Cov.: 30 AF XY: 0.466 AC XY: 34571 AN XY: 74138

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.461

Alfa AF: 0.454 Hom.: 7425

Bravo AF: 0.469

Asia WGS AF: 0.569 AC: 1980 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	2.8
DANN	Benign	0.66

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: rs950302; hg19: chr1-167083804;