Variant 2-190975250-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007315.4(STAT1):c.2136-318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 455,736 control chromosomes in the GnomAD database, including 10,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3508 hom., cov: 32)

Exomes 𝑓: 0.21 ( 7348 hom. )

Consequence

STAT1
NM_007315.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0310

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-190975250-C-T is Benign according to our data. Variant chr2-190975250-C-T is described in ClinVar as [Benign]. Clinvar id is 1264267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 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.2136-318G>A		intron_variant		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.2136-318G>A		intron_variant		1	NM_007315.4	ENSP00000354394	P4	P42224-1

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31647

AN:

151896

Hom.:

3508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.200

GnomAD4 exome

AF:

0.212

AC:

64482

AN:

303722

Hom.:

7348

AF XY:

0.211

AC XY:

35962

AN XY:

170218

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.327

Gnomad4 SAS exome

AF:

0.173

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.242

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.208

AC:

31647

AN:

152014

Hom.:

3508

Cov.:

AF XY:

0.202

AC XY:

15049

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.310

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.204

Alfa

AF:

0.209

Hom.:

723

Bravo

AF:

0.206

Asia WGS

AF:

0.243

AC:

846

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 30% of patients studied by a panel of primary immunodeficiencies. Number of patients: 26. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.3

DANN

Benign

0.73

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