rs4811191

Positions:

• chr20-51543496-G-A
• chr20-51543496-G-T

Variant summary

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

The ENST00000609943.5(NFATC2):​c.70+19064C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 152,280 control chromosomes in the GnomAD database, including 780 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 0.082 (780 hom., cov: 31)
• Consequence: NFATC2 ENST00000609943.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC2	NM_001136021.3	c.70+19064C>T		intron_variant
NFATC2	NM_001258292.2	c.70+19064C>T		intron_variant
NFATC2	NM_001258294.2	c.-14+19064C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC2	ENST00000414705.5	c.70+19064C>T		intron_variant		1
NFATC2	ENST00000609507.1	c.-14+19064C>T		intron_variant		1
NFATC2	ENST00000609943.5	c.70+19064C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12548 AN: 152160 Hom.: 782 Cov.: 31

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0822

Gnomad OTH AF: 0.0842

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

GnomAD4 genome AF: 0.0824 AC: 12542 AN: 152280 Hom.: 780 Cov.: 31 AF XY: 0.0870 AC XY: 6477 AN XY: 74454

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.0905

Gnomad4 NFE AF: 0.0821

Gnomad4 OTH AF: 0.0829

Alfa AF: 0.0842 Hom.: 635

Bravo AF: 0.0830

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4811191; hg19: chr20-50160035;