Variant chr18-79410428-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.875

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 1437 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC1	NM_001278669.2 linkuse as main transcript	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 linkuse as main transcript	c.153C>T	p.Asn51=	synonymous_variant	2/10	1	NM_001278669.2	P4	O95644-1

Frequencies

GnomAD3 genomes

AF:

0.00944

AC:

1436

AN:

152168

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00891

AC XY:

1190

AN XY:

133532

show subpopulations

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.:

AF XY:

0.0117

AC XY:

8482

AN XY:

725732

show subpopulations

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.:

Cov.:

AF XY:

0.00912

AC XY:

679

AN XY:

74486

show subpopulations

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.:

Bravo

AF:

0.00759

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0129

EpiControl

AF:

0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 06, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

NFATC1-related disorder

Benign:1

Benign, no assertion criteria provided

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over