rs6067803

chr20-51515460-T-G

Variant summary

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

The NM_012340.5(NFATC2):c.1332+1324A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,070 control chromosomes in the GnomAD database, including 16,033 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 0.46 (16033 hom., cov: 32)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC2	NM_012340.5	c.1332+1324A>C		intron_variant		ENST00000371564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC2	ENST00000371564.8	c.1332+1324A>C		intron_variant		1	NM_012340.5	A1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69376 AN: 151952 Hom.: 16040 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.456 AC: 69393 AN: 152070 Hom.: 16033 Cov.: 32 AF XY: 0.459 AC XY: 34095 AN XY: 74342

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.453

Alfa AF: 0.485 Hom.: 30428

Bravo AF: 0.446

Asia WGS AF: 0.457 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	14
Dann	Benign	0.64

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: rs6067803; hg19: chr20-50131999;