chr2-190990000-C-T

Variant names:

• chr2-190990000-C-T
• rs13005843
• NM_007315.4:c.1038-326G>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.1074-326G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.065 in 152,256 control chromosomes in the GnomAD database, including 376 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 0.065 (376 hom., cov: 33)
• Consequence: STAT1 NM_001384891.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 11 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 (AFR) allele frequency at 95% confidence interval = 0.0705 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT1	NM_007315.4	MANE Select	c.1038-326G>A		intron	N/A	NP_009330.1
	STAT1	NM_001384891.1		c.1074-326G>A		intron	N/A	NP_001371820.1
	STAT1	NM_001384886.1		c.1038-326G>A		intron	N/A	NP_001371815.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT1	ENST00000361099.8	TSL:1 MANE Select	c.1038-326G>A		intron	N/A	ENSP00000354394.4
	STAT1	ENST00000409465.5	TSL:1	c.1038-326G>A		intron	N/A	ENSP00000386244.1
	STAT1	ENST00000392322.7	TSL:1	c.1038-326G>A		intron	N/A	ENSP00000376136.3

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9891 AN: 152138 Hom.: 374 Cov.: 33

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.0976

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0287

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0721

Gnomad OTH AF: 0.0818

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

GnomAD4 genome AF: 0.0650 AC: 9904 AN: 152256 Hom.: 376 Cov.: 33 AF XY: 0.0626 AC XY: 4658 AN XY: 74430

African (AFR) AF: 0.0723 AC: 3002 AN: 41550

American (AMR) AF: 0.0646 AC: 988 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0976 AC: 339 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4828

European-Finnish (FIN) AF: 0.0287 AC: 304 AN: 10598

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0721 AC: 4906 AN: 68004

Other (OTH) AF: 0.0805 AC: 170 AN: 2112

Alfa AF: 0.0656 Hom.: 61

Bravo AF: 0.0712

Asia WGS AF: 0.0170 AC: 60 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	6.1
DANN	Benign	0.44
PhyloP100		0.11
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: rs13005843; hg19: chr2-191854726;