rs12590407

Positions:

• chr14-24365909-G-A
• chr14-24365909-G-T

Variant summary

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

The XR_007064085.1(LOC124903291):​n.758C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,134 control chromosomes in the GnomAD database, including 35,124 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 0.68 (35124 hom., cov: 33)
• Consequence: LOC124903291 XR_007064085.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

Genes affected

LOC124903291 (HGNC:):

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124903291	XR_007064085.1	n.758C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC4	ENST00000440487.6	n.46+191G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102962 AN: 152016 Hom.: 35083 Cov.: 33

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.671

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.677 AC: 103063 AN: 152134 Hom.: 35124 Cov.: 33 AF XY: 0.679 AC XY: 50505 AN XY: 74384

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.799

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.675

Alfa AF: 0.681 Hom.: 7331

Bravo AF: 0.661

Asia WGS AF: 0.716 AC: 2490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12590407; hg19: chr14-24835115;