rs2418736

chr16-68120959-G-A

Variant summary

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

The NM_173165.3(NFATC3):c.104-1028G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,758 control chromosomes in the GnomAD database, including 7,379 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 0.28 (7379 hom., cov: 31)
• Consequence: NFATC3 NM_173165.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913

Genes affected

NFATC3 (HGNC:7777): (nuclear factor of activated T cells 3) The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family participate to form this complex also. The product of this gene plays a role in the regulation of gene expression in T cells and immature thymocytes. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC3	NM_173165.3	c.104-1028G>A		intron_variant		ENST00000346183.8
NFATC3	NM_004555.4	c.104-1028G>A		intron_variant
NFATC3	NM_173163.3	c.104-1028G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC3	ENST00000346183.8	c.104-1028G>A		intron_variant		1	NM_173165.3	P3

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42070 AN: 151640 Hom.: 7348 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.278 AC: 42154 AN: 151758 Hom.: 7379 Cov.: 31 AF XY: 0.278 AC XY: 20593 AN XY: 74120

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.275

Alfa AF: 0.205 Hom.: 4601

Bravo AF: 0.284

Asia WGS AF: 0.253 AC: 881 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.9
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: rs2418736; hg19: chr16-68154862;