rs11697536

chr20-51491851-C-T

Variant summary

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

The NM_012340.5(NFATC2):c.1333-16191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 146,340 control chromosomes in the GnomAD database, including 120 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 0.033 (120 hom., cov: 29)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC2	NM_012340.5	c.1333-16191G>A		intron_variant		ENST00000371564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC2	ENST00000371564.8	c.1333-16191G>A		intron_variant		1	NM_012340.5	A1

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 4841 AN: 146226 Hom.: 121 Cov.: 29

Gnomad AFR AF: 0.00840

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.00427

Gnomad SAS AF: 0.0660

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.0654

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0399

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

GnomAD4 genome AF: 0.0331 AC: 4840 AN: 146340 Hom.: 120 Cov.: 29 AF XY: 0.0325 AC XY: 2311 AN XY: 71208

Gnomad4 AFR AF: 0.00838

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.0680

Gnomad4 EAS AF: 0.00407

Gnomad4 SAS AF: 0.0662

Gnomad4 FIN AF: 0.0196

Gnomad4 NFE AF: 0.0472

Gnomad4 OTH AF: 0.0395

Alfa AF: 0.0438 Hom.: 41

Bravo AF: 0.0309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.27
Dann	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11697536; hg19: chr20-50108389;