rs11848279

chr14-24379075-A-G

Variant summary

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

The NM_004554.5(NFATC4):c.*1370A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,178 control chromosomes in the GnomAD database, including 4,645 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 0.24 (4645 hom., cov: 32)
  • Exomes 𝑓: 0.21 (0 hom.)
• Consequence: NFATC4 NM_004554.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC4	NM_004554.5	c.*1370A>G		3_prime_UTR_variant	10/10	ENST00000250373.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC4	ENST00000250373.9	c.*1370A>G		3_prime_UTR_variant	10/10	1	NM_004554.5	P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36308 AN: 152018 Hom.: 4645 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.214 AC: 9 AN: 42 Hom.: 0 Cov.: 0 AF XY: 0.208 AC XY: 5 AN XY: 24

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.239 AC: 36326 AN: 152136 Hom.: 4645 Cov.: 32 AF XY: 0.244 AC XY: 18120 AN XY: 74382

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.213

Alfa AF: 0.223 Hom.: 6788

Bravo AF: 0.242

Asia WGS AF: 0.392 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	8.0
Dann	Benign	0.83

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: rs11848279; hg19: chr14-24848281;