chr2-191011343-G-A

Variant names:

• chr2-191011343-G-A
• rs16833172
• NM_007315.4:c.-1-1339C>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.-1-1339C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 152,188 control chromosomes in the GnomAD database, including 665 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 0.068 (665 hom., cov: 31)
• Consequence: STAT1 NM_007315.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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]

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 (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT1	NM_007315.4	c.-1-1339C>T		intron_variant	Intron 2 of 24	ENST00000361099.8	NP_009330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT1	ENST00000361099.8	c.-1-1339C>T		intron_variant	Intron 2 of 24	1	NM_007315.4	ENSP00000354394.4

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10360 AN: 152070 Hom.: 657 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.0602

Gnomad SAS AF: 0.0429

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0581

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

GnomAD4 genome AF: 0.0682 AC: 10384 AN: 152188 Hom.: 665 Cov.: 31 AF XY: 0.0676 AC XY: 5031 AN XY: 74414

African (AFR) AF: 0.149 AC: 6182 AN: 41480

American (AMR) AF: 0.130 AC: 1982 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3472

East Asian (EAS) AF: 0.0597 AC: 309 AN: 5174

South Asian (SAS) AF: 0.0427 AC: 206 AN: 4826

European-Finnish (FIN) AF: 0.0184 AC: 195 AN: 10604

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0183 AC: 1247 AN: 68028

Other (OTH) AF: 0.0575 AC: 121 AN: 2106

Alfa AF: 0.0500 Hom.: 96

Bravo AF: 0.0830

Asia WGS AF: 0.0820 AC: 284 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	4.2
DANN	Benign	0.75
PhyloP100		-0.35
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

Publications

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Other links and lift over

dbSNP: rs16833172; hg19: chr2-191876069;