chr2-190991275-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_007315.4(STAT1):c.990G>A(p.Gln330Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,614,146 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 21 hom. )

Consequence

STAT1
NM_007315.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.28

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 2-190991275-C-T is Benign according to our data. Variant chr2-190991275-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 333284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-190991275-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=3.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00313 (476/152278) while in subpopulation SAS AF= 0.0104 (50/4818). AF 95% confidence interval is 0.00809. There are 1 homozygotes in gnomad4. There are 250 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 21 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT1	NM_007315.4 link	c.990G>A	p.Gln330Gln	synonymous_variant	Exon 11 of 25	ENST00000361099.8	NP_009330.1	P42224-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT1	ENST00000361099.8 link	c.990G>A	p.Gln330Gln	synonymous_variant	Exon 11 of 25	1	NM_007315.4	ENSP00000354394.4		P42224-1

Frequencies

GnomAD3 genomes

AF:

0.00313

AC:

476

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0102

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00423

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00350

AC:

881

AN:

251462

Hom.:

AF XY:

0.00400

AC XY:

544

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00456

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00833

Gnomad FIN exome

AF:

0.00115

Gnomad NFE exome

AF:

0.00403

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00353

AC:

5164

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

2768

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00421

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00838

Gnomad4 FIN exome

AF:

0.00124

Gnomad4 NFE exome

AF:

0.00347

Gnomad4 OTH exome

AF:

0.00381

GnomAD4 genome

AF:

0.00313

AC:

476

AN:

152278

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

250

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00360

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00423

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00369

Hom.:

Bravo

AF:

0.00315

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00376

EpiControl

AF:

0.00415

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

STAT1: BP4, BS2 -

not specified

Benign:1

Aug 15, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-0.30

CADD

Benign

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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