rs17748980

Variant names:

• chr2-190966079-A-C
• rs17748980
• ENST00000673847.1:c.2238+8751T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-190966079-A-C
• chr2-190966079-A-G

Variant summary

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

The ENST00000673847.1(STAT1):​c.2238+8751T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,020 control chromosomes in the GnomAD database, including 11,925 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 0.38 (11925 hom., cov: 32)
• Consequence: STAT1 ENST00000673847.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000673847.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT1	ENST00000673847.1		c.2238+8751T>G		intron	N/A	ENSP00000501185.1
	STAT1	ENST00000673816.1		c.2238+8751T>G		intron	N/A	ENSP00000501127.1
	STAT1	ENST00000415035.2	TSL:3	n.*206-1385T>G		intron	N/A	ENSP00000388240.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57431 AN: 151902 Hom.: 11926 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.378 AC: 57428 AN: 152020 Hom.: 11925 Cov.: 32 AF XY: 0.380 AC XY: 28217 AN XY: 74312

African (AFR) AF: 0.261 AC: 10826 AN: 41478

American (AMR) AF: 0.294 AC: 4491 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3466

East Asian (EAS) AF: 0.103 AC: 532 AN: 5176

South Asian (SAS) AF: 0.342 AC: 1647 AN: 4820

European-Finnish (FIN) AF: 0.555 AC: 5842 AN: 10532

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31721 AN: 67960

Other (OTH) AF: 0.358 AC: 754 AN: 2106

Alfa AF: 0.409 Hom.: 16338

Bravo AF: 0.350

Asia WGS AF: 0.237 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.75
PhyloP100		-0.17

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17748980; hg19: chr2-191830805;