chr16-69596950-C-T

Variant names:

• chr16-69596950-C-T
• rs12447326
• NM_138713.4:c.127+28402C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138713.4(NFAT5):​c.127+28402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,718 control chromosomes in the GnomAD database, including 11,143 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 0.37 (11143 hom., cov: 30)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.127+28402C>T		intron_variant	Intron 2 of 14	ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7	c.127+28402C>T		intron_variant	Intron 2 of 14	1	NM_138713.4	ENSP00000338806.3

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55437 AN: 151600 Hom.: 11126 Cov.: 30

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.366 AC: 55504 AN: 151718 Hom.: 11143 Cov.: 30 AF XY: 0.368 AC XY: 27283 AN XY: 74128

African (AFR) AF: 0.528 AC: 21796 AN: 41306

American (AMR) AF: 0.417 AC: 6362 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3468

East Asian (EAS) AF: 0.451 AC: 2325 AN: 5160

South Asian (SAS) AF: 0.369 AC: 1776 AN: 4814

European-Finnish (FIN) AF: 0.260 AC: 2725 AN: 10494

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.272 AC: 18465 AN: 67914

Other (OTH) AF: 0.367 AC: 773 AN: 2108

Alfa AF: 0.317 Hom.: 17082

Bravo AF: 0.387

Asia WGS AF: 0.384 AC: 1335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.16
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12447326; hg19: chr16-69630853;