ENST00000609943.5:c.70+19064C>T

Variant names:

• chr20-51543496-G-A
• rs4811191
• ENST00000609943.5:c.70+19064C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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

ENSG00000304242 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NFATC2	NM_001258292.2	c.70+19064C>T		intron_variant	Intron 1 of 9		NP_001245221.1
NFATC2	NM_001136021.3	c.70+19064C>T		intron_variant	Intron 1 of 10		NP_001129493.1
NFATC2	NM_001258295.2	c.-14+19064C>T		intron_variant	Intron 1 of 9		NP_001245224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFATC2	ENST00000609943.5	c.70+19064C>T		intron_variant	Intron 1 of 9	1		ENSP00000477370.1
NFATC2	ENST00000414705.5	c.70+19064C>T		intron_variant	Intron 1 of 10	1		ENSP00000396471.1
NFATC2	ENST00000609507.1	c.-14+19064C>T		intron_variant	Intron 1 of 10	1		ENSP00000477342.1
ENSG00000304242	ENST00000801362.1	n.103+549G>A		intron_variant	Intron 1 of 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

African (AFR) AF: 0.0198 AC: 822 AN: 41574

American (AMR) AF: 0.141 AC: 2154 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3472

East Asian (EAS) AF: 0.212 AC: 1100 AN: 5192

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4814

European-Finnish (FIN) AF: 0.0905 AC: 960 AN: 10602

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0821 AC: 5588 AN: 68024

Other (OTH) AF: 0.0829 AC: 175 AN: 2112

Alfa AF: 0.0844 Hom.: 977

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
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4811191; hg19: chr20-50160035;