1-64942413-T-C

Position:

• chr1-64942413-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002227.4(JAK1):​c.-78+23920A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,112 control chromosomes in the GnomAD database, including 5,827 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 0.24 (5827 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: JAK1 NM_002227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

Genes affected

JAK1 (HGNC:6190): (Janus kinase 1) This gene encodes a membrane protein that is a member of a class of protein-tyrosine kinases (PTK) characterized by the presence of a second phosphotransferase-related domain immediately N-terminal to the PTK domain. The encoded kinase phosphorylates STAT proteins (signal transducers and activators of transcription) and plays a key role in interferon-alpha/beta, interferon-gamma, and cytokine signal transduction. This gene plays a crucial role in effecting the expression of genes that mediate inflammation, epithelial remodeling, and metastatic cancer progression. This gene is a key component of the interleukin-6 (IL-6)/JAK1/STAT3 immune and inflammation response and is a therapeutic target for alleviating cytokine storms. The kinase activity of this gene is directly inhibited by the suppressor of cytokine signalling 1 (SOCS1) protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2020]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAK1	NM_002227.4	c.-78+23920A>G		intron_variant		ENST00000342505.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAK1	ENST00000342505.5	c.-78+23920A>G		intron_variant		5	NM_002227.4	A1
	ENST00000446914.2			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36888 AN: 151994 Hom.: 5817 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.206

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.243 AC: 36931 AN: 152112 Hom.: 5827 Cov.: 32 AF XY: 0.250 AC XY: 18551 AN XY: 74348

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.203

Alfa AF: 0.144 Hom.: 1352

Bravo AF: 0.246

Asia WGS AF: 0.360 AC: 1248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.96

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

LitVar

Other links and lift over

dbSNP: rs7531799; hg19: chr1-65408096;