dbSNP rs2066805: STAT1:c.633+42A>G (chr2-190998175-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007315.4(STAT1):c.633+42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,585,260 control chromosomes in the GnomAD database, including 1,616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.029 ( 177 hom., cov: 32)

Exomes 𝑓: 0.027 ( 1439 hom. )

Consequence

STAT1
NM_007315.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.907

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-190998175-T-C is Benign according to our data. Variant chr2-190998175-T-C is described in ClinVar as [Benign]. Clinvar id is 2628271.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT1	NM_007315.4 link	c.633+42A>G		intron_variant	Intron 8 of 24	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.633+42A>G		intron_variant	Intron 8 of 24	1	NM_007315.4	ENSP00000354394.4		P42224-1

Frequencies

GnomAD3 genomes

AF:

0.0288

AC:

4388

AN:

152214

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.0634

Gnomad SAS

AF:

0.0450

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.0297

GnomAD3 exomes

AF:

0.0515

AC:

12896

AN:

250246

Hom.:

989

AF XY:

0.0454

AC XY:

6146

AN XY:

135370

show subpopulations

Gnomad AFR exome

AF:

0.0133

Gnomad AMR exome

AF:

0.209

Gnomad ASJ exome

AF:

0.0307

Gnomad EAS exome

AF:

0.0651

Gnomad SAS exome

AF:

0.0418

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.0195

Gnomad OTH exome

AF:

0.0449

GnomAD4 exome

AF:

0.0269

AC:

38584

AN:

1432928

Hom.:

1439

Cov.:

AF XY:

0.0267

AC XY:

19106

AN XY:

715034

show subpopulations

Gnomad4 AFR exome

AF:

0.0108

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.0295

Gnomad4 EAS exome

AF:

0.0500

Gnomad4 SAS exome

AF:

0.0425

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.0187

Gnomad4 OTH exome

AF:

0.0329

GnomAD4 genome

AF:

0.0288

AC:

4394

AN:

152332

Hom.:

177

Cov.:

AF XY:

0.0294

AC XY:

2190

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0141

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.0291

Gnomad4 EAS

AF:

0.0630

Gnomad4 SAS

AF:

0.0448

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.0183

Gnomad4 OTH

AF:

0.0294

Alfa

AF:

0.0269

Hom.:

Bravo

AF:

0.0375

Asia WGS

AF:

0.0690

AC:

240

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.73

DANN

Benign

0.58

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