NM_138713.4:c.1369+1787T>G

Variant names:

• chr16-69661686-T-G
• rs16959025
• NM_138713.4:c.1369+1787T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138713.4(NFAT5):​c.1369+1787T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 151,972 control chromosomes in the GnomAD database, including 2,208 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 (2208 hom., cov: 30)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.1369+1787T>G		intron_variant	Intron 7 of 14	ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7	c.1369+1787T>G		intron_variant	Intron 7 of 14	1	NM_138713.4	ENSP00000338806.3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23832 AN: 151854 Hom.: 2207 Cov.: 30

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.157 AC: 23843 AN: 151972 Hom.: 2208 Cov.: 30 AF XY: 0.161 AC XY: 11955 AN XY: 74270

African (AFR) AF: 0.0540 AC: 2242 AN: 41504

American (AMR) AF: 0.175 AC: 2663 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3470

East Asian (EAS) AF: 0.285 AC: 1468 AN: 5158

South Asian (SAS) AF: 0.310 AC: 1496 AN: 4820

European-Finnish (FIN) AF: 0.169 AC: 1775 AN: 10526

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12962 AN: 67954

Other (OTH) AF: 0.194 AC: 407 AN: 2102

Alfa AF: 0.175 Hom.: 1070

Bravo AF: 0.151

Asia WGS AF: 0.252 AC: 876 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.70
PhyloP100		1.3
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: rs16959025; hg19: chr16-69695589;