20-51538585-A-G

Position:

• chr20-51538585-A-G

Variant summary

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

The NM_012340.5(NFATC2):​c.130+3785T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,030 control chromosomes in the GnomAD database, including 14,223 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 0.43 (14223 hom., cov: 32)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC2	NM_012340.5	c.130+3785T>C		intron_variant		ENST00000371564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC2	ENST00000371564.8	c.130+3785T>C		intron_variant		1	NM_012340.5	A1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65368 AN: 151912 Hom.: 14208 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.430 AC: 65420 AN: 152030 Hom.: 14223 Cov.: 32 AF XY: 0.423 AC XY: 31410 AN XY: 74308

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.431

Alfa AF: 0.455 Hom.: 25983

Bravo AF: 0.429

Asia WGS AF: 0.258 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.72

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: rs6021275; hg19: chr20-50155124;