chr2-190971192-T-C

Position:

• chr2-190971192-T-C

Variant summary

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

The NM_007315.4(STAT1):​c.2239-475A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 152,172 control chromosomes in the GnomAD database, including 56,281 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 0.86 (56281 hom., cov: 31)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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 (NFE) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT1	NM_007315.4	c.2239-475A>G		intron_variant		ENST00000361099.8	NP_009330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT1	ENST00000361099.8	c.2239-475A>G		intron_variant		1	NM_007315.4	ENSP00000354394	P4

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130440 AN: 152054 Hom.: 56241 Cov.: 31

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.858 AC: 130538 AN: 152172 Hom.: 56281 Cov.: 31 AF XY: 0.860 AC XY: 63951 AN XY: 74372

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.939

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.834

Alfa AF: 0.880 Hom.: 19380

Bravo AF: 0.851

Asia WGS AF: 0.861 AC: 2996 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	0.071
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: rs7575823; hg19: chr2-191835918;