Variant chr2-190979104-A-G 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.1728-103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,473,594 control chromosomes in the GnomAD database, including 51,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4562 hom., cov: 32)

Exomes 𝑓: 0.26 ( 46874 hom. )

Consequence

STAT1
NM_007315.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.253

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-190979104-A-G is Benign according to our data. Variant chr2-190979104-A-G is described in ClinVar as [Benign]. Clinvar id is 1226208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT1	NM_007315.4 linkuse as main transcript	c.1728-103T>C		intron_variant		ENST00000361099.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT1	ENST00000361099.8 linkuse as main transcript	c.1728-103T>C		intron_variant		1	NM_007315.4	P4	P42224-1

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35759

AN:

152040

Hom.:

4564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.217

GnomAD4 exome

AF:

0.260

AC:

343578

AN:

1321436

Hom.:

46874

AF XY:

0.259

AC XY:

170846

AN XY:

658582

show subpopulations

Gnomad4 AFR exome

AF:

0.187

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.260

Gnomad4 EAS exome

AF:

0.543

Gnomad4 SAS exome

AF:

0.222

Gnomad4 FIN exome

AF:

0.242

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.255

GnomAD4 genome

AF:

0.235

AC:

35757

AN:

152158

Hom.:

4562

Cov.:

AF XY:

0.235

AC XY:

17462

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.204

Gnomad4 ASJ

AF:

0.271

Gnomad4 EAS

AF:

0.507

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.248

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.221

Alfa

AF:

0.220

Hom.:

463

Bravo

AF:

0.227

Asia WGS

AF:

0.376

AC:

1306

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

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.8

DANN

Benign

0.40

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