chr18-79396328-G-A

Position:

chr18-79396328-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001278669.2(NFATC1):c.104G>A(p.Gly35Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000993 in 1,405,140 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. G35G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0053 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 6 hom. )

Consequence

NFATC1
NM_001278669.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.12

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=0.002750963).

BP6

Variant 18-79396328-G-A is Benign according to our data. Variant chr18-79396328-G-A is described in ClinVar as [Benign]. Clinvar id is 712224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00528 (797/151082) while in subpopulation AFR AF= 0.0184 (758/41264). AF 95% confidence interval is 0.0173. There are 4 homozygotes in gnomad4. There are 381 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 797 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC1	NM_001278669.2 linkuse as main transcript	c.104G>A	p.Gly35Asp	missense_variant	1/10	ENST00000427363.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC1	ENST00000427363.7 linkuse as main transcript	c.104G>A	p.Gly35Asp	missense_variant	1/10	1	NM_001278669.2	P4	O95644-1

Frequencies

GnomAD3 genomes

AF:

0.00520

AC:

785

AN:

150976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00624

GnomAD3 exomes

AF:

0.000693

AC:

AN:

96634

Hom.:

AF XY:

0.000460

AC XY:

AN XY:

54326

show subpopulations

Gnomad AFR exome

AF:

0.0250

Gnomad AMR exome

AF:

0.000900

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000580

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000411

GnomAD4 exome

AF:

0.000477

AC:

598

AN:

1254058

Hom.:

Cov.:

AF XY:

0.000409

AC XY:

253

AN XY:

617976

show subpopulations

Gnomad4 AFR exome

AF:

0.0191

Gnomad4 AMR exome

AF:

0.00135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000502

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00528

AC:

797

AN:

151082

Hom.:

Cov.:

AF XY:

0.00516

AC XY:

381

AN XY:

73884

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00618

Alfa

AF:

0.000570

Hom.:

Bravo

AF:

0.00634

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000964

AC:

100

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

.;.;T;.;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.50

T;T;T;T;T

MetaRNN

Benign

0.0028

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.69

N;N;.;N;N

MutationTaster

Benign

1.0

D;N;N;N;N;N

PROVEAN

Benign

-0.090

N;.;.;N;.

REVEL

Benign

0.022

Sift

Uncertain

0.010

D;.;.;D;.

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.27

.;.;.;.;B

Vest4

0.084

MVP

0.17

ClinPred

0.011

GERP RS

1.3

Varity_R

0.12

gMVP

0.16

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