2-190986920-C-T

Position:

chr2-190986920-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_007315.4(STAT1):c.1155G>A(p.Thr385Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 1,614,156 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 27 hom. )

Consequence

STAT1
NM_007315.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.709

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:

STAT1 (HGNC:):

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=-0.72).

BP6

Variant 2-190986920-C-T is Benign according to our data. Variant chr2-190986920-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 333279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-190986920-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.709 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00286 (436/152278) while in subpopulation SAS AF= 0.00518 (25/4826). AF 95% confidence interval is 0.0036. There are 1 homozygotes in gnomad4. There are 211 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 27 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT1	NM_007315.4 linkuse as main transcript	c.1155G>A	p.Thr385Thr	synonymous_variant	14/25	ENST00000361099.8	NP_009330.1	P42224-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT1	ENST00000361099.8 linkuse as main transcript	c.1155G>A	p.Thr385Thr	synonymous_variant	14/25	1	NM_007315.4	ENSP00000354394.4		P42224-1

Frequencies

GnomAD3 genomes

AF:

0.00286

AC:

435

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00275

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00416

AC:

1046

AN:

251400

Hom.:

AF XY:

0.00446

AC XY:

606

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.0226

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00627

Gnomad FIN exome

AF:

0.00337

Gnomad NFE exome

AF:

0.00362

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00377

AC:

5507

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00382

AC XY:

2779

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.0238

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00636

Gnomad4 FIN exome

AF:

0.00348

Gnomad4 NFE exome

AF:

0.00323

Gnomad4 OTH exome

AF:

0.00493

GnomAD4 genome

AF:

0.00286

AC:

436

AN:

152278

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

211

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.00275

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00415

Hom.:

Bravo

AF:

0.00259

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00371

EpiControl

AF:

0.00391

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	STAT1: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 10, 2021

- -

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 29, 2024

- -

Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.63

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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