2-190975983-C-G

Position:

• chr2-190975983-C-G

Variant summary

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

The NM_007315.4(STAT1):​c.2060-96G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 1,116,890 control chromosomes in the GnomAD database, including 2,525 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 0.048 (257 hom., cov: 32)
  • Exomes 𝑓: 0.064 (2268 hom.)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT1	NM_007315.4	c.2060-96G>C		intron_variant		ENST00000361099.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT1	ENST00000361099.8	c.2060-96G>C		intron_variant		1	NM_007315.4	P4

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7246 AN: 152178 Hom.: 257 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0453

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0336

GnomAD4 exome AF: 0.0643 AC: 61977 AN: 964594 Hom.: 2268 AF XY: 0.0637 AC XY: 31583 AN XY: 495836

Gnomad4 AFR exome AF: 0.0115

Gnomad4 AMR exome AF: 0.0271

Gnomad4 ASJ exome AF: 0.0500

Gnomad4 EAS exome AF: 0.000201

Gnomad4 SAS exome AF: 0.0400

Gnomad4 FIN exome AF: 0.0429

Gnomad4 NFE exome AF: 0.0767

Gnomad4 OTH exome AF: 0.0573

GnomAD4 genome AF: 0.0476 AC: 7243 AN: 152296 Hom.: 257 Cov.: 32 AF XY: 0.0458 AC XY: 3413 AN XY: 74476

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.0320

Gnomad4 ASJ AF: 0.0453

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0356

Gnomad4 FIN AF: 0.0418

Gnomad4 NFE AF: 0.0780

Gnomad4 OTH AF: 0.0332

Alfa AF: 0.0689 Hom.: 44

Bravo AF: 0.0442

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.43

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: rs17749316; hg19: chr2-191840709;