chr2-190987171-G-A

Variant names:

• chr2-190987171-G-A
• rs2066795
• NM_007315.4:c.1098-103C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007315.4(STAT1):​c.1098-103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 887,266 control chromosomes in the GnomAD database, including 10,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2874 hom., cov: 32)
  • Exomes 𝑓: 0.13 (7162 hom.)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.521
• Publications: 12 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 2-190987171-G-A is Benign according to our data. Variant chr2-190987171-G-A is described in ClinVar as Benign. ClinVar VariationId is 1297899.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT1	NM_007315.4	c.1098-103C>T		intron_variant	Intron 12 of 24	ENST00000361099.8	NP_009330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT1	ENST00000361099.8	c.1098-103C>T		intron_variant	Intron 12 of 24	1	NM_007315.4	ENSP00000354394.4

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26879 AN: 151942 Hom.: 2862 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0710

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.131 AC: 96000 AN: 735206 Hom.: 7162 AF XY: 0.131 AC XY: 51050 AN XY: 388546

African (AFR) AF: 0.284 AC: 4960 AN: 17476

American (AMR) AF: 0.233 AC: 7477 AN: 32094

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 2889 AN: 20512

East Asian (EAS) AF: 0.137 AC: 4552 AN: 33232

South Asian (SAS) AF: 0.154 AC: 9776 AN: 63676

European-Finnish (FIN) AF: 0.0720 AC: 3386 AN: 47016

Middle Eastern (MID) AF: 0.186 AC: 493 AN: 2648

European-Non Finnish (NFE) AF: 0.119 AC: 57332 AN: 482816

Other (OTH) AF: 0.144 AC: 5135 AN: 35736

GnomAD4 genome AF: 0.177 AC: 26920 AN: 152060 Hom.: 2874 Cov.: 32 AF XY: 0.175 AC XY: 12983 AN XY: 74338

African (AFR) AF: 0.286 AC: 11836 AN: 41448

American (AMR) AF: 0.217 AC: 3320 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3468

East Asian (EAS) AF: 0.158 AC: 816 AN: 5180

South Asian (SAS) AF: 0.152 AC: 731 AN: 4810

European-Finnish (FIN) AF: 0.0710 AC: 752 AN: 10586

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8447 AN: 67962

Other (OTH) AF: 0.173 AC: 365 AN: 2112

Alfa AF: 0.149 Hom.: 2273

Bravo AF: 0.196

Asia WGS AF: 0.162 AC: 568 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.82
DANN	Benign	0.75
PhyloP100		-0.52
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: rs2066795; hg19: chr2-191851897;