rs2161630

Positions:

• chr16-69572558-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.127+4010G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,832 control chromosomes in the GnomAD database, including 24,003 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 0.55 (24003 hom., cov: 32)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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]

NFAT5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.127+4010G>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.127+4010G>A		intron_variant		1	NM_138713.4	ENSP00000338806.3

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82640 AN: 151714 Hom.: 23953 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.545 AC: 82761 AN: 151832 Hom.: 24003 Cov.: 32 AF XY: 0.548 AC XY: 40629 AN XY: 74168

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.531

Alfa AF: 0.468 Hom.: 7709

Bravo AF: 0.561

Asia WGS AF: 0.627 AC: 2156 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	9.3
DANN	Benign	0.45

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: rs2161630; hg19: chr16-69606461;