Variant 18-79396364-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001278669.2(NFATC1):c.127+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,308,984 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 28 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 29 hom. )

Consequence

NFATC1
NM_001278669.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.538

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 18-79396364-C-T is Benign according to our data. Variant chr18-79396364-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1629614.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1650/151500) while in subpopulation AFR AF= 0.0375 (1551/41406). AF 95% confidence interval is 0.0359. There are 28 homozygotes in gnomad4. There are 793 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1650 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC1	NM_001278669.2 linkuse as main transcript	c.127+13C>T		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+13C>T		intron_variant		1	NM_001278669.2	P4	O95644-1

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1647

AN:

151392

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0375

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00506

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00528

GnomAD3 exomes

AF:

0.00105

AC:

AN:

58322

Hom.:

AF XY:

0.000644

AC XY:

AN XY:

34160

show subpopulations

Gnomad AFR exome

AF:

0.0419

Gnomad AMR exome

AF:

0.00230

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000869

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000151

Gnomad OTH exome

AF:

0.00284

GnomAD4 exome

AF:

0.00113

AC:

1308

AN:

1157484

Hom.:

Cov.:

AF XY:

0.000956

AC XY:

539

AN XY:

563552

show subpopulations

Gnomad4 AFR exome

AF:

0.0427

Gnomad4 AMR exome

AF:

0.00319

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000134

Gnomad4 OTH exome

AF:

0.00267

GnomAD4 genome

AF:

0.0109

AC:

1650

AN:

151500

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

793

AN XY:

74070

show subpopulations

Gnomad4 AFR

AF:

0.0375

Gnomad4 AMR

AF:

0.00505

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000148

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00888

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.000585

AC:

AN:

3432

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.96

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