chr2-190975250-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, Orphanet
immunodeficiency 31B
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

STAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
STAT1	NM_007315.4 link	c.2136-318G>A		intron_variant	Intron 23 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.2136-318G>A		intron_variant	Intron 23 of 24	1	NM_007315.4	ENSP00000354394.4		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

African (AFR)

AF:

0.166

AC:

1305

AN:

7880

American (AMR)

AF:

0.120

AC:

2475

AN:

20540

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

1984

AN:

8736

East Asian (EAS)

AF:

0.327

AC:

3538

AN:

10810

South Asian (SAS)

AF:

0.173

AC:

9141

AN:

52986

European-Finnish (FIN)

AF:

0.144

AC:

3831

AN:

26576

Middle Eastern (MID)

AF:

0.208

AC:

559

AN:

2690

European-Non Finnish (NFE)

AF:

0.242

AC:

38633

AN:

159348

Other (OTH)

AF:

0.213

AC:

3016

AN:

14156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3118

6237

9355

12474

15592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.208

AC:

31647

AN:

152014

Hom.:

3508

Cov.:

AF XY:

0.202

AC XY:

15049

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.169

AC:

7002

AN:

41458

American (AMR)

AF:

0.167

AC:

2556

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

836

AN:

3472

East Asian (EAS)

AF:

0.310

AC:

1596

AN:

5154

South Asian (SAS)

AF:

0.174

AC:

840

AN:

4816

European-Finnish (FIN)

AF:

0.156

AC:

1648

AN:

10576

Middle Eastern (MID)

AF:

0.188

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.242

AC:

16427

AN:

67946

Other (OTH)

AF:

0.204

AC:

431

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1254

2508

3761

5015

6269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.209

Hom.:

739

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 24, 2024

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 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

(source)

DANN

Benign

0.73

PhyloP100

-0.031

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over