rs13010343

Positions:

• chr2-190978719-G-A

Variant summary

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

The NM_007315.4(STAT1):​c.1873+137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,069,436 control chromosomes in the GnomAD database, including 7,328 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 0.10 (884 hom., cov: 32)
  • Exomes 𝑓: 0.11 (6444 hom.)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT1	NM_007315.4	c.1873+137C>T		intron_variant		ENST00000361099.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT1	ENST00000361099.8	c.1873+137C>T		intron_variant		1	NM_007315.4	P4

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15537 AN: 152062 Hom.: 881 Cov.: 32

Gnomad AFR AF: 0.0768

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.111 AC: 101791 AN: 917256 Hom.: 6444 Cov.: 12 AF XY: 0.108 AC XY: 50411 AN XY: 465432

Gnomad4 AFR exome AF: 0.0779

Gnomad4 AMR exome AF: 0.0693

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.000423

Gnomad4 SAS exome AF: 0.0390

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.102 AC: 15559 AN: 152180 Hom.: 884 Cov.: 32 AF XY: 0.0999 AC XY: 7428 AN XY: 74376

Gnomad4 AFR AF: 0.0772

Gnomad4 AMR AF: 0.0886

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.112

Alfa AF: 0.125 Hom.: 1414

Bravo AF: 0.104

Asia WGS AF: 0.0320 AC: 112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.68

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: rs13010343; hg19: chr2-191843445;