Variant 18-79400407-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000427363.7(NFATC1):c.127+4056G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,342,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

NFATC1
ENST00000427363.7 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21160659).

BS2

High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFATC1	NM_001278669.2 linkuse as main transcript	c.127+4056G>A		intron_variant		ENST00000427363.7	NP_001265598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFATC1	ENST00000427363.7 linkuse as main transcript	c.127+4056G>A		intron_variant		1	NM_001278669.2	ENSP00000389377	P4	O95644-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000203

AC:

AN:

98416

Hom.:

AF XY:

0.0000182

AC XY:

AN XY:

54970

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000115

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1342810

Hom.:

Cov.:

AF XY:

0.0000181

AC XY:

AN XY:

662564

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000256

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000190

Gnomad4 OTH exome

AF:

0.0000182

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000241

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

Mar 14, 2023

The c.16G>A (p.D6N) alteration is located in exon 1 (coding exon 1) of the NFATC1 gene. This alteration results from a G to A substitution at nucleotide position 16, causing the aspartic acid (D) at amino acid position 6 to be replaced by an asparagine (N). 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

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.070

Eigen_PC

Benign

0.015

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.58

T;T;T;T

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.21

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

0.92

PROVEAN

Benign

-0.18

.;.;N;.

REVEL

Benign

0.077

Sift

Benign

0.31

.;.;T;.

Sift4G

Benign

0.17

T;T;T;T

Vest4

0.18

MutPred

0.27

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);

MVP

0.35

MPC

0.51

ClinPred

0.64

GERP RS

3.4

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