rs12693591

chr2-190995776-C-Achr2-190995776-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007315.4(STAT1):c.786-557G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,112 control chromosomes in the GnomAD database, including 5,518 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (5518 hom., cov: 31)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT1	NM_007315.4	c.786-557G>T		intron_variant		ENST00000361099.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT1	ENST00000361099.8	c.786-557G>T		intron_variant		1	NM_007315.4	P4

Frequencies

GnomAD3 genomes AF: 0.230 AC: 35013 AN: 151992 Hom.: 5489 Cov.: 31

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.0714

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.231 AC: 35089 AN: 152112 Hom.: 5518 Cov.: 31 AF XY: 0.229 AC XY: 17023 AN XY: 74396

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.0714

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.217

Alfa AF: 0.150 Hom.: 1306

Bravo AF: 0.256

Asia WGS AF: 0.238 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.3
Dann	Benign	0.55

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: rs12693591; hg19: chr2-191860502;