Variant 18-79486406-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001278669.2(NFATC1):c.2251T>G(p.Cys751Gly) variant causes a missense change. The variant allele was found at a frequency of 0.438 in 1,612,454 control chromosomes in the GnomAD database, including 158,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.38 ( 12087 hom., cov: 33)

Exomes 𝑓: 0.44 ( 146215 hom. )

Consequence

NFATC1
NM_001278669.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.90

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010785162).

BP6

Variant 18-79486406-T-G is Benign according to our data. Variant chr18-79486406-T-G is described in ClinVar as [Benign]. Clinvar id is 1640667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-79486406-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFATC1	NM_001278669.2 link	c.2251T>G	p.Cys751Gly	missense_variant	9/10	ENST00000427363.7	NP_001265598.1	O95644-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFATC1	ENST00000427363.7 link	c.2251T>G	p.Cys751Gly	missense_variant	9/10	1	NM_001278669.2	ENSP00000389377.2		O95644-1

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57478

AN:

151872

Hom.:

12095

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.355

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.462

Gnomad OTH

AF:

0.431

GnomAD3 exomes

AF:

0.424

AC:

106033

AN:

250046

Hom.:

23432

AF XY:

0.432

AC XY:

58459

AN XY:

135414

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.403

Gnomad ASJ exome

AF:

0.499

Gnomad EAS exome

AF:

0.345

Gnomad SAS exome

AF:

0.395

Gnomad FIN exome

AF:

0.484

Gnomad NFE exome

AF:

0.467

Gnomad OTH exome

AF:

0.465

GnomAD4 exome

AF:

0.444

AC:

647999

AN:

1460464

Hom.:

146215

Cov.:

AF XY:

0.445

AC XY:

323042

AN XY:

726536

show subpopulations

Gnomad4 AFR exome

AF:

0.181

Gnomad4 AMR exome

AF:

0.407

Gnomad4 ASJ exome

AF:

0.497

Gnomad4 EAS exome

AF:

0.376

Gnomad4 SAS exome

AF:

0.397

Gnomad4 FIN exome

AF:

0.476

Gnomad4 NFE exome

AF:

0.456

Gnomad4 OTH exome

AF:

0.433

GnomAD4 genome

AF:

0.378

AC:

57472

AN:

151990

Hom.:

12087

Cov.:

AF XY:

0.383

AC XY:

28420

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.443

Gnomad4 ASJ

AF:

0.489

Gnomad4 EAS

AF:

0.356

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.475

Gnomad4 NFE

AF:

0.462

Gnomad4 OTH

AF:

0.429

Alfa

AF:

0.454

Hom.:

20781

Bravo

AF:

0.369

TwinsUK

AF:

0.463

AC:

1715

ALSPAC

AF:

0.456

AC:

1758

ESP6500AA

AF:

0.183

AC:

808

ESP6500EA

AF:

0.463

AC:

3984

ExAC

AF:

0.415

AC:

50385

Asia WGS

AF:

0.340

AC:

1184

AN:

3478

EpiCase

AF:

0.479

EpiControl

AF:

0.487

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Feb 04, 2025	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Pathogenic

0.80

.;.;D;.;.;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.21

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.47

T;T;T;T;T;T

MetaRNN

Benign

0.0011

T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.8

M;.;M;.;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-5.1

D;D;.;D;.;D

REVEL

Benign

0.10

Sift

Uncertain

0.010

D;D;.;D;.;D

Sift4G

Uncertain

0.0070

D;D;D;D;D;D

Polyphen

0.87

.;.;P;.;.;.

Vest4

0.35

MPC

0.47

ClinPred

0.067

GERP RS

3.5

Varity_R

0.72

gMVP

0.42

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