rs2066802

Positions:

chr2-191009941-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007315.4(STAT1):c.63T>C(p.Leu21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.07 in 1,613,936 control chromosomes in the GnomAD database, including 5,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 472 hom., cov: 32)

Exomes 𝑓: 0.070 ( 4868 hom. )

Consequence

STAT1
NM_007315.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.410

Variant links:

Genes affected

STAT1 (HGNC:11362): (signal transducer and activator of transcription 1) The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. The protein encoded by this gene can be activated by various ligands including interferon-alpha, interferon-gamma, EGF, PDGF and IL6. This protein mediates the expression of a variety of genes, which is thought to be important for cell viability in response to different cell stimuli and pathogens. The protein plays an important role in immune responses to viral, fungal and mycobacterial pathogens. Mutations in this gene are associated with Immunodeficiency 31B, 31A, and 31C. [provided by RefSeq, Jun 2020]

STAT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 2-191009941-A-G is Benign according to our data. Variant chr2-191009941-A-G is described in ClinVar as [Benign]. Clinvar id is 333293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-191009941-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT1	NM_007315.4 linkuse as main transcript	c.63T>C	p.Leu21=	synonymous_variant	3/25	ENST00000361099.8	NP_009330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT1	ENST00000361099.8 linkuse as main transcript	c.63T>C	p.Leu21=	synonymous_variant	3/25	1	NM_007315.4	ENSP00000354394	P4	P42224-1

Frequencies

GnomAD3 genomes

AF:

0.0704

AC:

10713

AN:

152086

Hom.:

469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0743

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0496

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.0388

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0589

Gnomad OTH

AF:

0.0684

GnomAD3 exomes

AF:

0.0831

AC:

20892

AN:

251436

Hom.:

1271

AF XY:

0.0881

AC XY:

11968

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0762

Gnomad AMR exome

AF:

0.0419

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.224

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.0340

Gnomad NFE exome

AF:

0.0597

Gnomad OTH exome

AF:

0.0795

GnomAD4 exome

AF:

0.0700

AC:

102293

AN:

1461732

Hom.:

4868

Cov.:

AF XY:

0.0735

AC XY:

53467

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.0804

Gnomad4 AMR exome

AF:

0.0436

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.0365

Gnomad4 NFE exome

AF:

0.0578

Gnomad4 OTH exome

AF:

0.0810

GnomAD4 genome

AF:

0.0705

AC:

10725

AN:

152204

Hom.:

472

Cov.:

AF XY:

0.0714

AC XY:

5314

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0745

Gnomad4 AMR

AF:

0.0495

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.0388

Gnomad4 NFE

AF:

0.0589

Gnomad4 OTH

AF:

0.0687

Alfa

AF:

0.0632

Hom.:

426

Bravo

AF:

0.0699

Asia WGS

AF:

0.190

AC:

661

AN:

3478

EpiCase

AF:

0.0608

EpiControl

AF:

0.0604

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Immunodeficiency 31B;C3279990:Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome;C4013950:Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.9

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over