rs6013193

chr20-51475490-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012340.5(NFATC2):c.1503A>C(p.Ile501=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,613,548 control chromosomes in the GnomAD database, including 188,046 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 0.53 (23004 hom., cov: 30)
  • Exomes 𝑓: 0.47 (165042 hom.)
• Consequence: NFATC2 NM_012340.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130

Genes affected

NFATC2 (HGNC:7776): (nuclear factor of activated T cells 2) This gene is a member of the nuclear factor of activated T cells (NFAT) family. The product of this gene is a DNA-binding protein with a REL-homology region (RHR) and an NFAT-homology region (NHR). This protein is present in the cytosol and only translocates to the nucleus upon T cell receptor (TCR) stimulation, where it becomes a member of the nuclear factors of activated T cells transcription complex. This complex plays a central role in inducing gene transcription during the immune response. Alternate transcriptional splice variants encoding different isoforms have been characterized. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC2	NM_012340.5	c.1503A>C	p.Ile501=	synonymous_variant	4/11	ENST00000371564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC2	ENST00000371564.8	c.1503A>C	p.Ile501=	synonymous_variant	4/11	1	NM_012340.5	A1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80787 AN: 151696 Hom.: 22955 Cov.: 30

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.532

GnomAD3 exomes AF: 0.471 AC: 118513 AN: 251466 Hom.: 29082 AF XY: 0.465 AC XY: 63224 AN XY: 135902

Gnomad AFR exome AF: 0.747

Gnomad AMR exome AF: 0.522

Gnomad ASJ exome AF: 0.566

Gnomad EAS exome AF: 0.377

Gnomad SAS exome AF: 0.431

Gnomad FIN exome AF: 0.322

Gnomad NFE exome AF: 0.463

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.471 AC: 688940 AN: 1461734 Hom.: 165042 Cov.: 61 AF XY: 0.470 AC XY: 341768 AN XY: 727174

Gnomad4 AFR exome AF: 0.752

Gnomad4 AMR exome AF: 0.518

Gnomad4 ASJ exome AF: 0.569

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.329

Gnomad4 NFE exome AF: 0.471

Gnomad4 OTH exome AF: 0.489

GnomAD4 genome AF: 0.533 AC: 80884 AN: 151814 Hom.: 23004 Cov.: 30 AF XY: 0.524 AC XY: 38871 AN XY: 74184

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.530

Alfa AF: 0.506 Hom.: 11020

Bravo AF: 0.557

Asia WGS AF: 0.432 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	4.4
Dann	Benign	0.74

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: rs6013193; hg19: chr20-50092027; COSMIC: COSV65356048;