18-79410428-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001278669.2(NFATC1):c.153C>T(p.Asn51=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,611,122 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (15 hom., cov: 32)
  • Exomes 𝑓: 0.012 (143 hom.)
• Consequence: NFATC1 NM_001278669.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.875

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 18-79410428-C-T is Benign according to our data. Variant chr18-79410428-C-T is described in ClinVar as [Benign]. Clinvar id is 789237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.875 with no splicing effect.
• BS2: High AC in GnomAd at 1436 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC1	NM_001278669.2	c.153C>T	p.Asn51=	synonymous_variant	2/10	ENST00000427363.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC1	ENST00000427363.7	c.153C>T	p.Asn51=	synonymous_variant	2/10	1	NM_001278669.2	P4

Frequencies

GnomAD3 genomes AF: 0.00944 AC: 1436 AN: 152168 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.00671

GnomAD3 exomes AF: 0.00880 AC: 2170 AN: 246618 Hom.: 26 AF XY: 0.00891 AC XY: 1190 AN XY: 133532

Gnomad AFR exome AF: 0.00211

Gnomad AMR exome AF: 0.00259

Gnomad ASJ exome AF: 0.00112

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000658

Gnomad FIN exome AF: 0.0139

Gnomad NFE exome AF: 0.0152

Gnomad OTH exome AF: 0.00763

GnomAD4 exome AF: 0.0119 AC: 17415 AN: 1458836 Hom.: 143 Cov.: 30 AF XY: 0.0117 AC XY: 8482 AN XY: 725732

Gnomad4 AFR exome AF: 0.00179

Gnomad4 AMR exome AF: 0.00273

Gnomad4 ASJ exome AF: 0.00100

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000721

Gnomad4 FIN exome AF: 0.0156

Gnomad4 NFE exome AF: 0.0142

Gnomad4 OTH exome AF: 0.00917

GnomAD4 genome AF: 0.00944 AC: 1437 AN: 152286 Hom.: 15 Cov.: 32 AF XY: 0.00912 AC XY: 679 AN XY: 74486

Gnomad4 AFR AF: 0.00192

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0162

Gnomad4 NFE AF: 0.0151

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.0101 Hom.: 7

Bravo AF: 0.00759

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0129

EpiControl AF: 0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 06, 2024

- -

NFATC1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.0
Dann	Benign	0.46

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: rs150374931; hg19: chr18-77170428; COSMIC: COSV99502841;