rs244415

Positions:

• chr16-69632780-G-A

Variant summary

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

The NM_138713.4(NFAT5):​c.253+6252G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,928 control chromosomes in the GnomAD database, including 9,653 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 0.34 (9653 hom., cov: 31)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148

Genes affected

NFAT5 (HGNC:7774): (nuclear factor of activated T cells 5) The product of this gene is a member of the nuclear factors of activated T cells family of transcription factors. Proteins belonging to this family play a central role in inducible gene transcription during the immune response. This protein regulates gene expression induced by osmotic stress in mammalian cells. Unlike monomeric members of this protein family, this protein exists as a homodimer and forms stable dimers with DNA elements. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFAT5	NM_138713.4	c.253+6252G>A		intron_variant		ENST00000349945.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFAT5	ENST00000349945.7	c.253+6252G>A		intron_variant		1	NM_138713.4	A2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52067 AN: 151810 Hom.: 9664 Cov.: 31

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.343 AC: 52061 AN: 151928 Hom.: 9653 Cov.: 31 AF XY: 0.342 AC XY: 25364 AN XY: 74208

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.346

Alfa AF: 0.379 Hom.: 2322

Bravo AF: 0.329

Asia WGS AF: 0.269 AC: 937 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.58

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: rs244415; hg19: chr16-69666683;