2-190973478-C-T

Variant names:

• chr2-190973478-C-T
• rs6718902
• NM_007315.4:c.2238+1352G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384891.1(STAT1):​c.2274+1352G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,996 control chromosomes in the GnomAD database, including 4,134 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 0.22 (4134 hom., cov: 31)
• Consequence: STAT1 NM_001384891.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 24 publications found

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]

STAT1 Gene-Disease associations (from GenCC):

• autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, Orphanet
• immunodeficiency 31B

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384891.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT1	NM_007315.4	MANE Select	c.2238+1352G>A		intron	N/A	NP_009330.1
	STAT1	NM_001384891.1		c.2274+1352G>A		intron	N/A	NP_001371820.1
	STAT1	NM_001384886.1		c.2262+1352G>A		intron	N/A	NP_001371815.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT1	ENST00000361099.8	TSL:1 MANE Select	c.2238+1352G>A		intron	N/A	ENSP00000354394.4
	STAT1	ENST00000409465.5	TSL:1	c.2238+1352G>A		intron	N/A	ENSP00000386244.1
	STAT1	ENST00000673847.1		c.2238+1352G>A		intron	N/A	ENSP00000501185.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34116 AN: 151876 Hom.: 4137 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.224 AC: 34119 AN: 151996 Hom.: 4134 Cov.: 31 AF XY: 0.222 AC XY: 16527 AN XY: 74282

African (AFR) AF: 0.175 AC: 7251 AN: 41448

American (AMR) AF: 0.171 AC: 2605 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 955 AN: 3464

East Asian (EAS) AF: 0.461 AC: 2383 AN: 5168

South Asian (SAS) AF: 0.181 AC: 870 AN: 4816

European-Finnish (FIN) AF: 0.246 AC: 2593 AN: 10550

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16715 AN: 67970

Other (OTH) AF: 0.213 AC: 449 AN: 2112

Alfa AF: 0.230 Hom.: 2365

Bravo AF: 0.216

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.27
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6718902; hg19: chr2-191838204;