rs9889219

Positions:

• chr16-69687512-G-A
• chr16-69687512-G-T

Variant summary

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

The NM_138713.4(NFAT5):​c.1774+2542G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 150,444 control chromosomes in the GnomAD database, including 6,877 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 0.29 (6877 hom., cov: 29)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.1774+2542G>A		intron_variant		ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7	c.1774+2542G>A		intron_variant		1	NM_138713.4	ENSP00000338806	A2

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43384 AN: 150348 Hom.: 6848 Cov.: 29

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.300

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.289 AC: 43458 AN: 150444 Hom.: 6877 Cov.: 29 AF XY: 0.287 AC XY: 21054 AN XY: 73374

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.271

Alfa AF: 0.255 Hom.: 10379

Bravo AF: 0.289

Asia WGS AF: 0.298 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.30

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: rs9889219; hg19: chr16-69721415;