rs1547550

Variant names:

• chr2-190980999-C-G
• rs1547550
• NM_007315.4:c.1583-330G>C

Variant summary

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

The NM_007315.4(STAT1):​c.1583-330G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,924 control chromosomes in the GnomAD database, including 14,887 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 0.43 (14887 hom., cov: 31)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 18 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT1	NM_007315.4	c.1583-330G>C		intron_variant	Intron 18 of 24	ENST00000361099.8	NP_009330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT1	ENST00000361099.8	c.1583-330G>C		intron_variant	Intron 18 of 24	1	NM_007315.4	ENSP00000354394.4

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64609 AN: 151806 Hom.: 14863 Cov.: 31

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.426 AC: 64677 AN: 151924 Hom.: 14887 Cov.: 31 AF XY: 0.428 AC XY: 31820 AN XY: 74270

African (AFR) AF: 0.490 AC: 20267 AN: 41390

American (AMR) AF: 0.526 AC: 8031 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1150 AN: 3470

East Asian (EAS) AF: 0.889 AC: 4600 AN: 5174

South Asian (SAS) AF: 0.471 AC: 2269 AN: 4818

European-Finnish (FIN) AF: 0.334 AC: 3526 AN: 10542

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23521 AN: 67948

Other (OTH) AF: 0.413 AC: 872 AN: 2110

Alfa AF: 0.380 Hom.: 1448

Bravo AF: 0.444

Asia WGS AF: 0.649 AC: 2259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.62
PhyloP100		-0.69
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: rs1547550; hg19: chr2-191845725;