NM_001278669.2:c.127+6362T>C

Variant names:

• chr18-79402713-T-C
• rs2850724
• NM_001278669.2:c.127+6362T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

NFATC1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278669.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC1	NM_001278669.2	MANE Select	c.127+6362T>C		intron	N/A	NP_001265598.1	O95644-1
	NFATC1	NM_172387.3		c.88+2234T>C		intron	N/A	NP_765975.1	O95644-6
	NFATC1	NM_006162.5		c.127+6362T>C		intron	N/A	NP_006153.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC1	ENST00000427363.7	TSL:1 MANE Select	c.127+6362T>C		intron	N/A	ENSP00000389377.2	O95644-1
	NFATC1	ENST00000329101.8	TSL:1	c.88+2234T>C		intron	N/A	ENSP00000327850.3	O95644-6
	NFATC1	ENST00000253506.9	TSL:1	c.127+6362T>C		intron	N/A	ENSP00000253506.5	O95644-4

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

African (AFR) AF: 0.912 AC: 37891 AN: 41548

American (AMR) AF: 0.909 AC: 13916 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2689 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5167 AN: 5170

South Asian (SAS) AF: 0.964 AC: 4661 AN: 4834

European-Finnish (FIN) AF: 0.956 AC: 10151 AN: 10616

Middle Eastern (MID) AF: 0.815 AC: 238 AN: 292

European-Non Finnish (NFE) AF: 0.901 AC: 61290 AN: 68034

Other (OTH) AF: 0.892 AC: 1887 AN: 2116

Alfa AF: 0.897 Hom.: 111902

Bravo AF: 0.906

Asia WGS AF: 0.977 AC: 3395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.096
DANN	Benign	0.41
PhyloP100		-3.7
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: rs2850724; hg19: chr18-77162713;