rs1064825

Variant names:

• chr16-69690317-G-A
• rs1064825
• NM_138713.4:c.1775-623G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-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 rank	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.1775-623G>A		intron_variant	Intron 11 of 14	ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7	c.1775-623G>A		intron_variant	Intron 11 of 14	1	NM_138713.4	ENSP00000338806.3

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

African (AFR) AF: 0.0102 AC: 419 AN: 41202

American (AMR) AF: 0.0441 AC: 671 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.0532 AC: 184 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.0403 AC: 193 AN: 4786

European-Finnish (FIN) AF: 0.0827 AC: 836 AN: 10106

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0564 AC: 3816 AN: 67692

Other (OTH) AF: 0.0573 AC: 120 AN: 2094

Alfa AF: 0.0501 Hom.: 163

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
PhyloP100		0.65
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: rs1064825; hg19: chr16-69724220;