14-24376196-G-T

Position:

• chr14-24376196-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004554.5(NFATC4):​c.2056+95G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,589,074 control chromosomes in the GnomAD database, including 3,126 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.045 (340 hom., cov: 31)
  • Exomes 𝑓: 0.042 (2786 hom.)
• Consequence: NFATC4 NM_004554.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

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]

NFATC4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFATC4	NM_004554.5	c.2056+95G>T		intron_variant		ENST00000250373.9	NP_004545.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFATC4	ENST00000250373.9	c.2056+95G>T		intron_variant		1	NM_004554.5	ENSP00000250373.4

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6837 AN: 152038 Hom.: 341 Cov.: 31

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0567

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0316

GnomAD4 exome AF: 0.0417 AC: 59895 AN: 1436918 Hom.: 2786 Cov.: 34 AF XY: 0.0443 AC XY: 31509 AN XY: 711876

Gnomad4 AFR exome AF: 0.0418

Gnomad4 AMR exome AF: 0.0414

Gnomad4 ASJ exome AF: 0.0149

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.0568

Gnomad4 NFE exome AF: 0.0269

Gnomad4 OTH exome AF: 0.0494

GnomAD4 genome AF: 0.0449 AC: 6831 AN: 152156 Hom.: 340 Cov.: 31 AF XY: 0.0494 AC XY: 3677 AN XY: 74392

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0567

Gnomad4 NFE AF: 0.0261

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0210 Hom.: 12

Bravo AF: 0.0412

Asia WGS AF: 0.198 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.016
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs10141896; hg19: chr14-24845402; COSMIC: COSV51598086; COSMIC: COSV51598086;