rs754505

Variant names:

• chr18-79466368-G-A
• rs754505
• NM_001278669.2:c.1960-1082G>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.1960-1082G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0585 in 152,220 control chromosomes in the GnomAD database, including 325 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 0.058 (325 hom., cov: 33)
• Consequence: NFATC1 NM_001278669.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFATC1	NM_001278669.2	c.1960-1082G>A		intron_variant	Intron 7 of 9	ENST00000427363.7	NP_001265598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFATC1	ENST00000427363.7	c.1960-1082G>A		intron_variant	Intron 7 of 9	1	NM_001278669.2	ENSP00000389377.2

Frequencies

GnomAD3 genomes AF: 0.0585 AC: 8901 AN: 152102 Hom.: 325 Cov.: 33

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0622

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0585 AC: 8898 AN: 152220 Hom.: 325 Cov.: 33 AF XY: 0.0595 AC XY: 4426 AN XY: 74424

African (AFR) AF: 0.0139 AC: 576 AN: 41554

American (AMR) AF: 0.0553 AC: 846 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 315 AN: 3470

East Asian (EAS) AF: 0.0999 AC: 516 AN: 5164

South Asian (SAS) AF: 0.132 AC: 637 AN: 4818

European-Finnish (FIN) AF: 0.0622 AC: 659 AN: 10600

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0736 AC: 5006 AN: 68000

Other (OTH) AF: 0.0668 AC: 141 AN: 2112

Alfa AF: 0.0707 Hom.: 654

Bravo AF: 0.0545

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.72
DANN	Benign	0.54
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs754505; hg19: chr18-77226368;