chr16-69690317-G-A

Position:

• chr16-69690317-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.1775-623G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 150,908 control chromosomes in the GnomAD database, including 177 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 0.042 (177 hom., cov: 32)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.649

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 = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.1775-623G>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.1775-623G>A		intron_variant		1	NM_138713.4	ENSP00000338806	A2

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6331 AN: 150798 Hom.: 177 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0442

Gnomad ASJ AF: 0.0532

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0398

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0584

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

GnomAD4 genome AF: 0.0419 AC: 6329 AN: 150908 Hom.: 177 Cov.: 32 AF XY: 0.0430 AC XY: 3168 AN XY: 73662

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.0441

Gnomad4 ASJ AF: 0.0532

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0403

Gnomad4 FIN AF: 0.0827

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0573

Alfa AF: 0.0502 Hom.: 136

Bravo AF: 0.0376

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.15

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: rs1064825; hg19: chr16-69724220;