chr16-69612219-C-T

Variant names:

• chr16-69612219-C-T
• rs11639947
• NM_138713.4:c.128-14184C>T

Variant summary

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

The NM_138713.4(NFAT5):​c.128-14184C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,036 control chromosomes in the GnomAD database, including 3,957 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 0.22 (3957 hom., cov: 32)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.128-14184C>T		intron_variant	Intron 2 of 14	ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7	c.128-14184C>T		intron_variant	Intron 2 of 14	1	NM_138713.4	ENSP00000338806.3

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33261 AN: 151918 Hom.: 3950 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.219 AC: 33294 AN: 152036 Hom.: 3957 Cov.: 32 AF XY: 0.225 AC XY: 16733 AN XY: 74296

African (AFR) AF: 0.187 AC: 7766 AN: 41476

American (AMR) AF: 0.329 AC: 5027 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2315 AN: 5162

South Asian (SAS) AF: 0.336 AC: 1620 AN: 4820

European-Finnish (FIN) AF: 0.191 AC: 2019 AN: 10554

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13166 AN: 67960

Other (OTH) AF: 0.239 AC: 503 AN: 2106

Alfa AF: 0.206 Hom.: 9351

Bravo AF: 0.230

Asia WGS AF: 0.331 AC: 1148 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	4.9
DANN	Benign	0.94
PhyloP100		-0.75
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: rs11639947; hg19: chr16-69646122;