chr18-79400428-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_172387.3(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. 12/19 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
NM_172387.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.112

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

NFATC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High AC in GnomAd4 at 68 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172387.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFATC1	NM_001278669.2	MANE Select	c.127+4077T>A		intron	N/A	NP_001265598.1	O95644-1
NFATC1	NM_172387.3		c.37T>A	p.Phe13Ile	missense	Exon 1 of 10	NP_765975.1	O95644-6
NFATC1	NM_172389.3		c.37T>A	p.Phe13Ile	missense	Exon 1 of 10	NP_765977.1	O95644-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFATC1	ENST00000329101.8	TSL:1	c.37T>A	p.Phe13Ile	missense	Exon 1 of 10	ENSP00000327850.3	O95644-6
NFATC1	ENST00000318065.9	TSL:1	c.37T>A	p.Phe13Ile	missense	Exon 1 of 10	ENSP00000316553.5	O95644-5
NFATC1	ENST00000592223.5	TSL:1	c.37T>A	p.Phe13Ile	missense	Exon 1 of 8	ENSP00000467181.1	O95644-3

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

GnomAD2 exomes

AF:

0.000481

AC:

AN:

101848

AF XY:

0.000511

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 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

African (AFR)

AF:

0.0000371

AC:

AN:

26966

American (AMR)

AF:

0.000177

AC:

AN:

28254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23328

East Asian (EAS)

AF:

0.00

AC:

AN:

29164

South Asian (SAS)

AF:

0.000797

AC:

AN:

74064

European-Finnish (FIN)

AF:

0.000255

AC:

AN:

46988

Middle Eastern (MID)

AF:

0.00309

AC:

AN:

5500

European-Non Finnish (NFE)

AF:

0.000701

AC:

739

AN:

1054140

Other (OTH)

AF:

0.000635

AC:

AN:

55110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000450

AC:

AN:

151198

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

AN XY:

73890

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41330

American (AMR)

AF:

0.000197

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5012

South Asian (SAS)

AF:

0.000836

AC:

AN:

4786

European-Finnish (FIN)

AF:

0.000191

AC:

AN:

10450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000754

AC:

AN:

67608

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.94

Eigen

Benign

0.13

Eigen_PC

Benign

0.087

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.63

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

PhyloP100

0.11

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.43

REVEL

Benign

0.093

Sift

Benign

1.0

Sift4G

Benign

0.57

Vest4

0.51

MVP

0.42

MPC

0.50

ClinPred

0.041

GERP RS

3.4

PromoterAI

-0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=290/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over