18-79517719-G-A

Variant names:

• chr18-79517719-G-A
• rs12959273
• NM_001278669.2:c.2783-9809G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278669.2(NFATC1):​c.2783-9809G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,076 control chromosomes in the GnomAD database, including 8,600 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 0.33 (8600 hom., cov: 33)
• Consequence: NFATC1 NM_001278669.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFATC1	NM_001278669.2	c.2783-9809G>A		intron_variant	Intron 9 of 9	ENST00000427363.7	NP_001265598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFATC1	ENST00000427363.7	c.2783-9809G>A		intron_variant	Intron 9 of 9	1	NM_001278669.2	ENSP00000389377.2

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49898 AN: 151958 Hom.: 8600 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.328 AC: 49895 AN: 152076 Hom.: 8600 Cov.: 33 AF XY: 0.327 AC XY: 24302 AN XY: 74338

African (AFR) AF: 0.271 AC: 11247 AN: 41474

American (AMR) AF: 0.288 AC: 4409 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1171 AN: 3470

East Asian (EAS) AF: 0.138 AC: 712 AN: 5172

South Asian (SAS) AF: 0.271 AC: 1305 AN: 4820

European-Finnish (FIN) AF: 0.439 AC: 4634 AN: 10550

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25253 AN: 67984

Other (OTH) AF: 0.313 AC: 660 AN: 2112

Alfa AF: 0.343 Hom.: 20254

Bravo AF: 0.310

Asia WGS AF: 0.206 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.087
DANN	Benign	0.62
PhyloP100		-1.3
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: rs12959273; hg19: chr18-77277719;