rs2304526

Positions:

• chr16-69655447-A-G
• chr16-69655447-A-T

Variant summary

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

The NM_138713.4(NFAT5):​c.1006-162A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,894 control chromosomes in the GnomAD database, including 2,172 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 0.16 (2172 hom., cov: 31)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.920

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.1006-162A>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.1006-162A>G		intron_variant		1	NM_138713.4	ENSP00000338806	A2

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24586 AN: 151774 Hom.: 2167 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0972

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.162 AC: 24609 AN: 151894 Hom.: 2172 Cov.: 31 AF XY: 0.163 AC XY: 12126 AN XY: 74206

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0971

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.153

Alfa AF: 0.159 Hom.: 351

Bravo AF: 0.154

Asia WGS AF: 0.241 AC: 835 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.67

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: rs2304526; hg19: chr16-69689350;