rs1914408

chr2-190975250-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0310

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 Benign. Variant got -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 id 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/exons	MANE	UniProt
STAT1	NM_007315.4	c.2136-318G>A		intron_variant		ENST00000361099.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT1	ENST00000361099.8	c.2136-318G>A		intron_variant		1	NM_007315.4	P4

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31647 AN: 151896 Hom.: 3508 Cov.: 32

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

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.327

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.208 AC: 31647 AN: 152014 Hom.: 3508 Cov.: 32 AF XY: 0.202 AC XY: 15049 AN XY: 74330

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.204

Alfa AF: 0.209 Hom.: 723

Bravo AF: 0.206

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.3
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs1914408; hg19: chr2-191839976; COSMIC: COSV63114929; COSMIC: COSV63114929;