rs2280235

Variant names:

• chr2-190979104-A-G
• rs2280235
• NM_007315.4:c.1728-103T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-190979104-A-G
• chr2-190979104-A-C
• chr2-190979104-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.253
• Publications: 20 publications found

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: Illumina, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Ambry Genetics
• immunodeficiency 31B

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, Orphanet, G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007315.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT1	NM_007315.4	MANE Select	c.1728-103T>C		intron	N/A	NP_009330.1	P42224-1
	STAT1	NM_001384891.1		c.1764-103T>C		intron	N/A	NP_001371820.1
	STAT1	NM_001384886.1		c.1728-103T>C		intron	N/A	NP_001371815.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT1	ENST00000361099.8	TSL:1 MANE Select	c.1728-103T>C		intron	N/A	ENSP00000354394.4	P42224-1
	STAT1	ENST00000409465.5	TSL:1	c.1728-103T>C		intron	N/A	ENSP00000386244.1	P42224-1
	STAT1	ENST00000392322.7	TSL:1	c.1728-103T>C		intron	N/A	ENSP00000376136.3	P42224-2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35759 AN: 152040 Hom.: 4564 Cov.: 32

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

African (AFR) AF: 0.187 AC: 5660 AN: 30306

American (AMR) AF: 0.160 AC: 6074 AN: 38052

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 6462 AN: 24814

East Asian (EAS) AF: 0.543 AC: 20090 AN: 36978

South Asian (SAS) AF: 0.222 AC: 17474 AN: 78794

European-Finnish (FIN) AF: 0.242 AC: 11177 AN: 46212

Middle Eastern (MID) AF: 0.225 AC: 1249 AN: 5550

European-Non Finnish (NFE) AF: 0.260 AC: 261182 AN: 1005098

Other (OTH) AF: 0.255 AC: 14210 AN: 55632

GnomAD4 genome AF: 0.235 AC: 35757 AN: 152158 Hom.: 4562 Cov.: 32 AF XY: 0.235 AC XY: 17462 AN XY: 74400

African (AFR) AF: 0.185 AC: 7695 AN: 41514

American (AMR) AF: 0.204 AC: 3124 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3468

East Asian (EAS) AF: 0.507 AC: 2623 AN: 5174

South Asian (SAS) AF: 0.233 AC: 1124 AN: 4826

European-Finnish (FIN) AF: 0.248 AC: 2622 AN: 10578

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16852 AN: 67994

Other (OTH) AF: 0.221 AC: 468 AN: 2114

Alfa AF: 0.220 Hom.: 463

Bravo AF: 0.227

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.40
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2280235; hg19: chr2-191843830; COSMIC: COSV63117234; COSMIC: COSV63117234;