rs2066805

chr2-190998175-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007315.4(STAT1):c.633+42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,585,260 control chromosomes in the GnomAD database, including 1,616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (177 hom., cov: 32)
  • Exomes 𝑓: 0.027 (1439 hom.)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.907

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-190998175-T-C is Benign according to our data. Variant chr2-190998175-T-C is described in ClinVar as [Benign]. Clinvar id is 2628271.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT1	NM_007315.4	c.633+42A>G		intron_variant		ENST00000361099.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT1	ENST00000361099.8	c.633+42A>G		intron_variant		1	NM_007315.4	P4

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4388 AN: 152214 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.0634

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0297

GnomAD3 exomes AF: 0.0515 AC: 12896 AN: 250246 Hom.: 989 AF XY: 0.0454 AC XY: 6146 AN XY: 135370

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.209

Gnomad ASJ exome AF: 0.0307

Gnomad EAS exome AF: 0.0651

Gnomad SAS exome AF: 0.0418

Gnomad FIN exome AF: 0.0109

Gnomad NFE exome AF: 0.0195

Gnomad OTH exome AF: 0.0449

GnomAD4 exome AF: 0.0269 AC: 38584 AN: 1432928 Hom.: 1439 Cov.: 26 AF XY: 0.0267 AC XY: 19106 AN XY: 715034

Gnomad4 AFR exome AF: 0.0108

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.0295

Gnomad4 EAS exome AF: 0.0500

Gnomad4 SAS exome AF: 0.0425

Gnomad4 FIN exome AF: 0.0113

Gnomad4 NFE exome AF: 0.0187

Gnomad4 OTH exome AF: 0.0329

GnomAD4 genome AF: 0.0288 AC: 4394 AN: 152332 Hom.: 177 Cov.: 32 AF XY: 0.0294 AC XY: 2190 AN XY: 74500

Gnomad4 AFR AF: 0.0141

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.0630

Gnomad4 SAS AF: 0.0448

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0269 Hom.: 23

Bravo AF: 0.0375

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.73
Dann	Benign	0.58

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: rs2066805; hg19: chr2-191862901;