NM_007315.4:c.2060-96G>C

Variant names:

• chr2-190975983-C-G
• rs17749316
• NM_007315.4:c.2060-96G>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.2060-96G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 1,116,890 control chromosomes in the GnomAD database, including 2,525 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 0.048 (257 hom., cov: 32)
  • Exomes 𝑓: 0.064 (2268 hom.)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 9 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: Illumina, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

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

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, Orphanet, G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007315.4. 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.2060-96G>C		intron	N/A	NP_009330.1	P42224-1
	STAT1	NM_001384891.1		c.2096-96G>C		intron	N/A	NP_001371820.1
	STAT1	NM_001384886.1		c.2060-72G>C		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.2060-96G>C		intron	N/A	ENSP00000354394.4	P42224-1
	STAT1	ENST00000409465.5	TSL:1	c.2060-96G>C		intron	N/A	ENSP00000386244.1	P42224-1
	STAT1	ENST00000392322.7	TSL:1	c.2060-96G>C		intron	N/A	ENSP00000376136.3	P42224-2

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7246 AN: 152178 Hom.: 257 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0453

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0336

GnomAD4 exome AF: 0.0643 AC: 61977 AN: 964594 Hom.: 2268 AF XY: 0.0637 AC XY: 31583 AN XY: 495836

African (AFR) AF: 0.0115 AC: 268 AN: 23316

American (AMR) AF: 0.0271 AC: 999 AN: 36910

Ashkenazi Jewish (ASJ) AF: 0.0500 AC: 1135 AN: 22682

East Asian (EAS) AF: 0.000201 AC: 7 AN: 34744

South Asian (SAS) AF: 0.0400 AC: 2885 AN: 72118

European-Finnish (FIN) AF: 0.0429 AC: 2086 AN: 48680

Middle Eastern (MID) AF: 0.0270 AC: 131 AN: 4844

European-Non Finnish (NFE) AF: 0.0767 AC: 51956 AN: 677516

Other (OTH) AF: 0.0573 AC: 2510 AN: 43784

GnomAD4 genome AF: 0.0476 AC: 7243 AN: 152296 Hom.: 257 Cov.: 32 AF XY: 0.0458 AC XY: 3413 AN XY: 74476

African (AFR) AF: 0.0117 AC: 486 AN: 41572

American (AMR) AF: 0.0320 AC: 490 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0453 AC: 157 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0356 AC: 172 AN: 4830

European-Finnish (FIN) AF: 0.0418 AC: 444 AN: 10610

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0780 AC: 5308 AN: 68014

Other (OTH) AF: 0.0332 AC: 70 AN: 2108

Alfa AF: 0.0689 Hom.: 44

Bravo AF: 0.0442

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.43
PhyloP100		1.9
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: rs17749316; hg19: chr2-191840709;