rs13395505

Variant names:

• chr2-190973788-G-A
• rs13395505
• NM_007315.4:c.2238+1042C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-190973788-G-A
• chr2-190973788-G-C
• chr2-190973788-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007315.4(STAT1):​c.2238+1042C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,966 control chromosomes in the GnomAD database, including 13,128 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13128 hom., cov: 31)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452
• 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: 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT1	NM_007315.4	c.2238+1042C>T		intron_variant	Intron 24 of 24	ENST00000361099.8	NP_009330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT1	ENST00000361099.8	c.2238+1042C>T		intron_variant	Intron 24 of 24	1	NM_007315.4	ENSP00000354394.4

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62385 AN: 151848 Hom.: 13100 Cov.: 31

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.365

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.400

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.411 AC: 62461 AN: 151966 Hom.: 13128 Cov.: 31 AF XY: 0.407 AC XY: 30203 AN XY: 74244

African (AFR) AF: 0.450 AC: 18626 AN: 41426

American (AMR) AF: 0.352 AC: 5372 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1579 AN: 3464

East Asian (EAS) AF: 0.552 AC: 2856 AN: 5174

South Asian (SAS) AF: 0.352 AC: 1697 AN: 4820

European-Finnish (FIN) AF: 0.365 AC: 3850 AN: 10550

Middle Eastern (MID) AF: 0.368 AC: 106 AN: 288

European-Non Finnish (NFE) AF: 0.398 AC: 27067 AN: 67948

Other (OTH) AF: 0.404 AC: 854 AN: 2112

Alfa AF: 0.402 Hom.: 18036

Bravo AF: 0.413

Asia WGS AF: 0.484 AC: 1684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.44
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13395505; hg19: chr2-191838514;