2-191009591-G-T

Variant names:

• chr2-191009591-G-T
• rs41507345
• NM_007315.4:c.128+285C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007315.4(STAT1):​c.128+285C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 152,158 control chromosomes in the GnomAD database, including 303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.056 (303 hom., cov: 33)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.132
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-191009591-G-T is Benign according to our data. Variant chr2-191009591-G-T is described in ClinVar as Benign. ClinVar VariationId is 1286087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT1	NM_007315.4	c.128+285C>A		intron_variant	Intron 3 of 24	ENST00000361099.8	NP_009330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT1	ENST00000361099.8	c.128+285C>A		intron_variant	Intron 3 of 24	1	NM_007315.4	ENSP00000354394.4

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8501 AN: 152040 Hom.: 303 Cov.: 33

Gnomad AFR AF: 0.0551

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0356

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0362

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0512

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

GnomAD4 genome AF: 0.0559 AC: 8503 AN: 152158 Hom.: 303 Cov.: 33 AF XY: 0.0567 AC XY: 4221 AN XY: 74410

African (AFR) AF: 0.0550 AC: 2283 AN: 41498

American (AMR) AF: 0.0356 AC: 544 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.184 AC: 952 AN: 5174

South Asian (SAS) AF: 0.141 AC: 678 AN: 4820

European-Finnish (FIN) AF: 0.0362 AC: 383 AN: 10580

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0474 AC: 3224 AN: 68008

Other (OTH) AF: 0.0517 AC: 109 AN: 2110

Alfa AF: 0.0524 Hom.: 366

Bravo AF: 0.0549

Asia WGS AF: 0.154 AC: 537 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.39
PhyloP100		-0.13
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: rs41507345; hg19: chr2-191874317;