rs2850724

Positions:

• chr18-79402713-T-C

Variant summary

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

The NM_001278669.2(NFATC1):​c.127+6362T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 152,298 control chromosomes in the GnomAD database, including 63,248 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 0.91 (63248 hom., cov: 34)
• Consequence: NFATC1 NM_001278669.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.67

Genes affected

NFATC1 (HGNC:7775): (nuclear factor of activated T cells 1) The product of this gene is a component of the nuclear factor of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation, and an inducible nuclear component. Proteins belonging to this family of transcription factors play a central role in inducible gene transcription during immune response. The product of this gene is an inducible nuclear component. It functions as a major molecular target for the immunosuppressive drugs such as cyclosporin A. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Different isoforms of this protein may regulate inducible expression of different cytokine genes. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC1	NM_001278669.2	c.127+6362T>C		intron_variant		ENST00000427363.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC1	ENST00000427363.7	c.127+6362T>C		intron_variant		1	NM_001278669.2	P4

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138578 AN: 152180 Hom.: 63188 Cov.: 34

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.964

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.911 AC: 138696 AN: 152298 Hom.: 63248 Cov.: 34 AF XY: 0.913 AC XY: 67988 AN XY: 74468

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.909

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.964

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.901

Gnomad4 OTH AF: 0.892

Alfa AF: 0.895 Hom.: 80056

Bravo AF: 0.906

Asia WGS AF: 0.977 AC: 3395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.096
DANN	Benign	0.41

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: rs2850724; hg19: chr18-77162713;