rs4811172

Positions:

• chr20-51401774-G-A
• chr20-51401774-G-C
• chr20-51401774-G-T

Variant summary

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

The NM_012340.5(NFATC2):​c.2723-3044C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 152,234 control chromosomes in the GnomAD database, including 63,747 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 0.91 (63747 hom., cov: 32)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFATC2	NM_012340.5	c.2723-3044C>T		intron_variant		ENST00000371564.8	NP_036472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFATC2	ENST00000371564.8	c.2723-3044C>T		intron_variant		1	NM_012340.5	ENSP00000360619.3

Frequencies

GnomAD3 genomes AF: 0.915 AC: 139161 AN: 152116 Hom.: 63703 Cov.: 32

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.905

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

GnomAD4 genome AF: 0.915 AC: 139262 AN: 152234 Hom.: 63747 Cov.: 32 AF XY: 0.913 AC XY: 67974 AN XY: 74428

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.919

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.906

Gnomad4 OTH AF: 0.905

Alfa AF: 0.904 Hom.: 13914

Bravo AF: 0.917

Asia WGS AF: 0.953 AC: 3313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.043
DANN	Benign	0.20

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: rs4811172; hg19: chr20-50018311;