chr18-79516964-A-G

Variant names:

• chr18-79516964-A-G
• rs177820
• NM_001278669.2:c.2783-10564A>G

Variant summary

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

The NM_001278669.2(NFATC1):​c.2783-10564A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,098 control chromosomes in the GnomAD database, including 11,439 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 0.38 (11439 hom., cov: 33)
• Consequence: NFATC1 NM_001278669.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.680
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC1	NM_001278669.2	MANE Select	c.2783-10564A>G		intron	N/A	NP_001265598.1
	NFATC1	NM_172387.3		c.2744-10564A>G		intron	N/A	NP_765975.1
	NFATC1	NM_006162.5		c.2476-10564A>G		intron	N/A	NP_006153.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC1	ENST00000427363.7	TSL:1 MANE Select	c.2783-10564A>G		intron	N/A	ENSP00000389377.2
	NFATC1	ENST00000329101.8	TSL:1	c.2744-10564A>G		intron	N/A	ENSP00000327850.3
	NFATC1	ENST00000253506.9	TSL:1	c.2476-10564A>G		intron	N/A	ENSP00000253506.5

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57568 AN: 151978 Hom.: 11422 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.379 AC: 57618 AN: 152098 Hom.: 11439 Cov.: 33 AF XY: 0.381 AC XY: 28342 AN XY: 74372

African (AFR) AF: 0.342 AC: 14165 AN: 41456

American (AMR) AF: 0.439 AC: 6705 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1498 AN: 3472

East Asian (EAS) AF: 0.714 AC: 3693 AN: 5170

South Asian (SAS) AF: 0.548 AC: 2642 AN: 4822

European-Finnish (FIN) AF: 0.269 AC: 2851 AN: 10584

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24699 AN: 67986

Other (OTH) AF: 0.407 AC: 860 AN: 2114

Alfa AF: 0.375 Hom.: 17966

Bravo AF: 0.389

Asia WGS AF: 0.612 AC: 2125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.38
PhyloP100		-0.68
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: rs177820; hg19: chr18-77276964;