2-190987072-CA-CAA

Variant names:

• chr2-190987072-C-CA
• rs200288904
• NM_007315.4:c.1098-5dupT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_007315.4(STAT1):​c.1098-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000337 in 1,596,784 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: STAT1 NM_007315.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.27

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 2-190987072-C-CA is Benign according to our data. Variant chr2-190987072-C-CA is described in ClinVar as [Benign]. Clinvar id is 541831.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00137 (207/151524) while in subpopulation AFR AF= 0.00445 (184/41348). AF 95% confidence interval is 0.00392. There are 0 homozygotes in gnomad4. There are 99 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT1	NM_007315.4	c.1098-5dupT		splice_region_variant, intron_variant	Intron 12 of 24	ENST00000361099.8	NP_009330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT1	ENST00000361099.8	c.1098-5_1098-4insT		splice_region_variant, intron_variant	Intron 12 of 24	1	NM_007315.4	ENSP00000354394.4

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 207 AN: 151408 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00446

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000460

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.000357 AC: 87 AN: 243928 Hom.: 0 AF XY: 0.000257 AC XY: 34 AN XY: 132068

Gnomad AFR exome AF: 0.00416

Gnomad AMR exome AF: 0.000119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000337

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000146

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.000229 AC: 331 AN: 1445260 Hom.: 1 Cov.: 29 AF XY: 0.000210 AC XY: 151 AN XY: 719742

Gnomad4 AFR exome AF: 0.00406

Gnomad4 AMR exome AF: 0.000202

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000467

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000140

Gnomad4 OTH exome AF: 0.000436

GnomAD4 genome AF: 0.00137 AC: 207 AN: 151524 Hom.: 0 Cov.: 32 AF XY: 0.00134 AC XY: 99 AN XY: 74062

Gnomad4 AFR AF: 0.00445

Gnomad4 AMR AF: 0.000459

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00285

Bravo AF: 0.00159

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

STAT1-related disorder Benign:1

Jul 02, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Immunodeficiency 31B;C3279990:Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome;C4013950:Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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

Other links and lift over

dbSNP: rs200288904; hg19: chr2-191851798;