16-69620887-G-T

Variant names:

• chr16-69620887-G-T
• rs8049728
• NM_138713.4:c.128-5516G>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.128-5516G>T 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 152,028 control chromosomes in the GnomAD database, including 24,047 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 0.54 (24047 hom., cov: 32)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.128-5516G>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.128-5516G>T		intron_variant	Intron 2 of 14	1	NM_138713.4	ENSP00000338806.3

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82734 AN: 151906 Hom.: 23997 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.555

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: 82855 AN: 152028 Hom.: 24047 Cov.: 32 AF XY: 0.548 AC XY: 40699 AN XY: 74312

African (AFR) AF: 0.734 AC: 30443 AN: 41486

American (AMR) AF: 0.521 AC: 7963 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1663 AN: 3466

East Asian (EAS) AF: 0.814 AC: 4221 AN: 5188

South Asian (SAS) AF: 0.556 AC: 2677 AN: 4812

European-Finnish (FIN) AF: 0.434 AC: 4575 AN: 10542

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29630 AN: 67948

Other (OTH) AF: 0.531 AC: 1120 AN: 2110

Alfa AF: 0.503 Hom.: 3354

Bravo AF: 0.561

Asia WGS AF: 0.627 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.8
DANN	Benign	0.37
PhyloP100		-0.042
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: rs8049728; hg19: chr16-69654790;