rs1437137

Variant names:

• chr16-69670835-G-A
• rs1437137
• NM_138713.4:c.1557+547G>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.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 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• Publications: 8 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=-0.75).
• 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 rank	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.1557+547G>A		intron_variant	Intron 9 of 14	ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7	c.1557+547G>A		intron_variant	Intron 9 of 14	1	NM_138713.4	ENSP00000338806.3

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

African (AFR) AF: 0.0447 AC: 1855 AN: 41506

American (AMR) AF: 0.0509 AC: 778 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3468

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

South Asian (SAS) AF: 0.0253 AC: 122 AN: 4818

European-Finnish (FIN) AF: 0.0687 AC: 727 AN: 10582

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0734 AC: 4989 AN: 68016

Other (OTH) AF: 0.0638 AC: 135 AN: 2116

Alfa AF: 0.0661 Hom.: 133

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
PhyloP100		-0.60
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: rs1437137; hg19: chr16-69704738;