rs4809847

Variant names:

• chr20-51491782-G-T
• rs4809847
• NM_012340.5:c.1333-16122C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012340.5(NFATC2):​c.1333-16122C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 151,632 control chromosomes in the GnomAD database, including 888 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 0.095 (888 hom., cov: 30)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 6 publications found

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]

NFATC2 Gene-Disease associations (from GenCC):

• joint contractures, osteochondromas, and B-cell lymphoma

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFATC2	NM_012340.5	c.1333-16122C>A		intron_variant	Intron 3 of 10	ENST00000371564.8	NP_036472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFATC2	ENST00000371564.8	c.1333-16122C>A		intron_variant	Intron 3 of 10	1	NM_012340.5	ENSP00000360619.3

Frequencies

GnomAD3 genomes AF: 0.0945 AC: 14315 AN: 151514 Hom.: 881 Cov.: 30

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0507

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0946 AC: 14340 AN: 151632 Hom.: 888 Cov.: 30 AF XY: 0.0957 AC XY: 7086 AN XY: 74062

African (AFR) AF: 0.0388 AC: 1604 AN: 41350

American (AMR) AF: 0.153 AC: 2333 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3466

East Asian (EAS) AF: 0.0506 AC: 260 AN: 5134

South Asian (SAS) AF: 0.163 AC: 779 AN: 4776

European-Finnish (FIN) AF: 0.0985 AC: 1031 AN: 10472

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7542 AN: 67914

Other (OTH) AF: 0.102 AC: 215 AN: 2100

Alfa AF: 0.113 Hom.: 2219

Bravo AF: 0.0964

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
DANN	Benign	0.43
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4809847; hg19: chr20-50108320; COSMIC: COSV65361774;