rs6021231

Positions:

• chr20-51475750-T-C

Variant summary

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

The NM_012340.5(NFATC2):​c.1333-90A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,243,730 control chromosomes in the GnomAD database, including 142,667 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 0.51 (20664 hom., cov: 30)
  • Exomes 𝑓: 0.47 (122003 hom.)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFATC2	NM_012340.5	c.1333-90A>G		intron_variant		ENST00000371564.8	NP_036472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFATC2	ENST00000371564.8	c.1333-90A>G		intron_variant		1	NM_012340.5	ENSP00000360619.3

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77528 AN: 151798 Hom.: 20611 Cov.: 30

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.515

GnomAD4 exome AF: 0.470 AC: 512626 AN: 1091814 Hom.: 122003 AF XY: 0.468 AC XY: 256422 AN XY: 547422

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.565

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.437

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.489

GnomAD4 genome AF: 0.511 AC: 77625 AN: 151916 Hom.: 20664 Cov.: 30 AF XY: 0.503 AC XY: 37353 AN XY: 74236

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.514

Alfa AF: 0.479 Hom.: 23058

Bravo AF: 0.532

Asia WGS AF: 0.444 AC: 1542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.37

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: rs6021231; hg19: chr20-50092287; COSMIC: COSV65356629;