NM_007315.4:c.1873+137C>T

Variant names:

• chr2-190978719-G-A
• rs13010343
• NM_007315.4:c.1873+137C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.91).
• 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 rank	MANE	Protein	UniProt
STAT1	NM_007315.4	c.1873+137C>T		intron_variant	Intron 21 of 24	ENST00000361099.8	NP_009330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT1	ENST00000361099.8	c.1873+137C>T		intron_variant	Intron 21 of 24	1	NM_007315.4	ENSP00000354394.4

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

African (AFR) AF: 0.0779 AC: 1756 AN: 22536

American (AMR) AF: 0.0693 AC: 2408 AN: 34766

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3351 AN: 21964

East Asian (EAS) AF: 0.000423 AC: 14 AN: 33060

South Asian (SAS) AF: 0.0390 AC: 2680 AN: 68698

European-Finnish (FIN) AF: 0.112 AC: 4174 AN: 37194

Middle Eastern (MID) AF: 0.127 AC: 402 AN: 3154

European-Non Finnish (NFE) AF: 0.126 AC: 82285 AN: 653782

Other (OTH) AF: 0.112 AC: 4721 AN: 42102

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

African (AFR) AF: 0.0772 AC: 3206 AN: 41530

American (AMR) AF: 0.0886 AC: 1355 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4820

European-Finnish (FIN) AF: 0.106 AC: 1117 AN: 10578

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8666 AN: 67980

Other (OTH) AF: 0.112 AC: 238 AN: 2116

Alfa AF: 0.123 Hom.: 1684

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
PhyloP100		-2.7
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: rs13010343; hg19: chr2-191843445;