2-190977153-A-G

Position:

• chr2-190977153-A-G

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.1874-128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 862,766 control chromosomes in the GnomAD database, including 25,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4100 hom., cov: 32)
  • Exomes 𝑓: 0.23 (21464 hom.)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.350

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=-0.82).
• BP6: Variant 2-190977153-A-G is Benign according to our data. Variant chr2-190977153-A-G is described in ClinVar as [Benign]. Clinvar id is 1174479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT1	NM_007315.4	c.1874-128T>C		intron_variant		ENST00000361099.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT1	ENST00000361099.8	c.1874-128T>C		intron_variant		1	NM_007315.4	P4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33919 AN: 152086 Hom.: 4103 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.234 AC: 166617 AN: 710562 Hom.: 21464 AF XY: 0.234 AC XY: 88077 AN XY: 376624

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.502

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.223 AC: 33914 AN: 152204 Hom.: 4100 Cov.: 32 AF XY: 0.221 AC XY: 16425 AN XY: 74412

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.213

Alfa AF: 0.216 Hom.: 494

Bravo AF: 0.214

Asia WGS AF: 0.295 AC: 1025 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.41
DANN	Benign	0.44

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: rs7597768; hg19: chr2-191841879;