Variant chr18-79400428-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000329101.8(NFATC1):c.37T>A(p.Phe13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000626 in 1,494,712 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00065 ( 2 hom. )

Consequence

NFATC1
ENST00000329101.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.112

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05349019).

BS2

High AC in GnomAd4 at 68 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC1	NM_001278669.2 linkuse as main transcript	c.127+4077T>A		intron_variant		ENST00000427363.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC1	ENST00000427363.7 linkuse as main transcript	c.127+4077T>A		intron_variant		1	NM_001278669.2	P4	O95644-1

Frequencies

GnomAD3 genomes

AF:

0.000450

AC:

AN:

151090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000835

Gnomad FIN

AF:

0.000191

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000754

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000481

AC:

AN:

101848

Hom.:

AF XY:

0.000511

AC XY:

AN XY:

56740

show subpopulations

Gnomad AFR exome

AF:

0.000458

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000681

Gnomad FIN exome

AF:

0.0000685

Gnomad NFE exome

AF:

0.000877

Gnomad OTH exome

AF:

0.000371

GnomAD4 exome

AF:

0.000646

AC:

868

AN:

1343514

Hom.:

Cov.:

AF XY:

0.000673

AC XY:

446

AN XY:

662998

show subpopulations

Gnomad4 AFR exome

AF:

0.0000371

Gnomad4 AMR exome

AF:

0.000177

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000797

Gnomad4 FIN exome

AF:

0.000255

Gnomad4 NFE exome

AF:

0.000701

Gnomad4 OTH exome

AF:

0.000635

GnomAD4 genome

AF:

0.000450

AC:

AN:

151198

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

AN XY:

73890

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000836

Gnomad4 FIN

AF:

0.000191

Gnomad4 NFE

AF:

0.000754

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000429

Hom.:

Bravo

AF:

0.000427

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000273

AC:

ExAC

AF:

0.000180

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.37T>A (p.F13I) alteration is located in exon 1 (coding exon 1) of the NFATC1 gene. This alteration results from a T to A substitution at nucleotide position 37, causing the phenylalanine (F) at amino acid position 13 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

0.13

Eigen_PC

Benign

0.087

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.63

T;T;T;T

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.053

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;N;N;N;N

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.43

.;.;N;.

REVEL

Benign

0.093

Sift

Benign

1.0

.;.;T;.

Sift4G

Benign

0.57

T;T;T;T

Vest4

0.51

MVP

0.42

MPC

0.50

ClinPred

0.041

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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