rs1437137

Positions:

• chr16-69670835-G-A

Variant summary

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

The ENST00000349945.7(NFAT5):​c.1557+547G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0592 in 152,154 control chromosomes in the GnomAD database, including 287 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 0.059 (287 hom., cov: 32)
• Consequence: NFAT5 ENST00000349945.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600

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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.1557+547G>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.1557+547G>A		intron_variant		1	NM_138713.4	ENSP00000338806	A2

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 8997 AN: 152036 Hom.: 286 Cov.: 32

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.0687

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0640

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

GnomAD4 genome AF: 0.0592 AC: 9009 AN: 152154 Hom.: 287 Cov.: 32 AF XY: 0.0577 AC XY: 4295 AN XY: 74410

Gnomad4 AFR AF: 0.0447

Gnomad4 AMR AF: 0.0509

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0253

Gnomad4 FIN AF: 0.0687

Gnomad4 NFE AF: 0.0734

Gnomad4 OTH AF: 0.0638

Alfa AF: 0.0655 Hom.: 121

Bravo AF: 0.0590

Asia WGS AF: 0.0180 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.6
DANN	Benign	0.77

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: rs1437137; hg19: chr16-69704738;