rs2066795

Positions:

• chr2-190987171-G-A

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.1098-103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 887,266 control chromosomes in the GnomAD database, including 10,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2874 hom., cov: 32)
  • Exomes 𝑓: 0.13 (7162 hom.)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.521

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=-0.74).
• BP6: Variant 2-190987171-G-A is Benign according to our data. Variant chr2-190987171-G-A is described in ClinVar as [Benign]. Clinvar id is 1297899.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT1	NM_007315.4	c.1098-103C>T		intron_variant		ENST00000361099.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT1	ENST00000361099.8	c.1098-103C>T		intron_variant		1	NM_007315.4	P4

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26879 AN: 151942 Hom.: 2862 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0710

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.131 AC: 96000 AN: 735206 Hom.: 7162 AF XY: 0.131 AC XY: 51050 AN XY: 388546

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.0720

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.177 AC: 26920 AN: 152060 Hom.: 2874 Cov.: 32 AF XY: 0.175 AC XY: 12983 AN XY: 74338

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0710

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.173

Alfa AF: 0.141 Hom.: 1498

Bravo AF: 0.196

Asia WGS AF: 0.162 AC: 568 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.82
DANN	Benign	0.75

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: rs2066795; hg19: chr2-191851897;