rs16959025

chr16-69661686-T-G

Variant summary

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

The NM_138713.4(NFAT5):c.1369+1787T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 151,972 control chromosomes in the GnomAD database, including 2,208 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 0.16 (2208 hom., cov: 30)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFAT5	NM_138713.4	c.1369+1787T>G		intron_variant		ENST00000349945.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFAT5	ENST00000349945.7	c.1369+1787T>G		intron_variant		1	NM_138713.4	A2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23832 AN: 151854 Hom.: 2207 Cov.: 30

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.157 AC: 23843 AN: 151972 Hom.: 2208 Cov.: 30 AF XY: 0.161 AC XY: 11955 AN XY: 74270

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.194

Alfa AF: 0.169 Hom.: 582

Bravo AF: 0.151

Asia WGS AF: 0.252 AC: 876 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.4
Dann	Benign	0.70

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: rs16959025; hg19: chr16-69695589;