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GeneBe

14-24369722-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_004554.5(NFATC4):c.324C>T(p.Gly108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,584,444 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0081 ( 15 hom., cov: 33)
Exomes 𝑓: 0.0010 ( 16 hom. )

Consequence

NFATC4
NM_004554.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.30
Variant links:
Genes affected
NFATC4 (HGNC:7778): (nuclear factor of activated T cells 4) This gene encodes a member of the nuclear factor of activated T cells (NFAT) protein family. The encoded protein is part of a 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 stimulation and an inducible nuclear component. NFAT proteins are activated by the calmodulin-dependent phosphatase, calcineurin. The encoded protein plays a role in the inducible expression of cytokine genes in T cells, especially in the induction of interleukin-2 and interleukin-4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-24369722-C-T is Benign according to our data. Variant chr14-24369722-C-T is described in ClinVar as [Benign]. Clinvar id is 778738.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.3 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00806 (1212/150352) while in subpopulation AFR AF= 0.0269 (1117/41460). AF 95% confidence interval is 0.0256. There are 15 homozygotes in gnomad4. There are 565 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1213 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NFATC4NM_004554.5 linkuse as main transcriptc.324C>T p.Gly108= synonymous_variant 2/10 ENST00000250373.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NFATC4ENST00000250373.9 linkuse as main transcriptc.324C>T p.Gly108= synonymous_variant 2/101 NM_004554.5 P1Q14934-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00807
AC:
1213
AN:
150232
Hom.:
15
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0270
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00357
Gnomad ASJ
AF:
0.000587
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000212
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00327
Gnomad NFE
AF:
0.000330
Gnomad OTH
AF:
0.00730
GnomAD3 exomes
AF:
0.00244
AC:
572
AN:
234280
Hom.:
8
AF XY:
0.00169
AC XY:
215
AN XY:
127524
show subpopulations
Gnomad AFR exome
AF:
0.0281
Gnomad AMR exome
AF:
0.00241
Gnomad ASJ exome
AF:
0.00129
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000239
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000465
Gnomad OTH exome
AF:
0.00176
GnomAD4 exome
AF:
0.00103
AC:
1472
AN:
1434092
Hom.:
16
Cov.:
38
AF XY:
0.000939
AC XY:
669
AN XY:
712668
show subpopulations
Gnomad4 AFR exome
AF:
0.0251
Gnomad4 AMR exome
AF:
0.00276
Gnomad4 ASJ exome
AF:
0.00122
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000237
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000253
Gnomad4 OTH exome
AF:
0.00267
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00806
AC:
1212
AN:
150352
Hom.:
15
Cov.:
33
AF XY:
0.00768
AC XY:
565
AN XY:
73582
show subpopulations
Gnomad4 AFR
AF:
0.0269
Gnomad4 AMR
AF:
0.00356
Gnomad4 ASJ
AF:
0.000587
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000212
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000330
Gnomad4 OTH
AF:
0.00723
Alfa
AF:
0.00149
Hom.:
0
Bravo
AF:
0.00911
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
8.7
Dann
Benign
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs114908477; hg19: chr14-24838928; API