chr16-69619793-C-G

Position:

• chr16-69619793-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138713.4(NFAT5):​c.128-6610C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,190 control chromosomes in the GnomAD database, including 60,617 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 0.89 (60617 hom., cov: 31)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.128-6610C>G		intron_variant		ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7	c.128-6610C>G		intron_variant		1	NM_138713.4	ENSP00000338806	A2

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135518 AN: 152072 Hom.: 60561 Cov.: 31

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.891 AC: 135632 AN: 152190 Hom.: 60617 Cov.: 31 AF XY: 0.893 AC XY: 66461 AN XY: 74410

Gnomad4 AFR AF: 0.959

Gnomad4 AMR AF: 0.873

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.882

Alfa AF: 0.875 Hom.: 7261

Bravo AF: 0.893

Asia WGS AF: 0.897 AC: 3122 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	0.77
DANN	Benign	0.41

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: rs39999; hg19: chr16-69653696;