rs6751855

Positions:

• chr2-191020045-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000454414.5(STAT1):​c.-2+155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,090 control chromosomes in the GnomAD database, including 14,683 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 0.39 (14683 hom., cov: 33)
• Consequence: STAT1 ENST00000454414.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT1	ENST00000432058.1	c.-156+713C>T		intron_variant		4		ENSP00000416019
STAT1	ENST00000454414.5	c.-2+155C>T		intron_variant		4		ENSP00000411398

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59533 AN: 151972 Hom.: 14680 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.391 AC: 59540 AN: 152090 Hom.: 14683 Cov.: 33 AF XY: 0.395 AC XY: 29403 AN XY: 74368

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.378

Alfa AF: 0.492 Hom.: 8975

Bravo AF: 0.361

Asia WGS AF: 0.301 AC: 1042 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.7
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6751855; hg19: chr2-191884771;