chr16-69614592-T-C

Variant names:

• chr16-69614592-T-C
• rs7198242
• NM_138713.4:c.128-11811T>C

Variant summary

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

The NM_138713.4(NFAT5):​c.128-11811T>C 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 152,158 control chromosomes in the GnomAD database, including 3,972 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 (3972 hom., cov: 31)
• Consequence: NFAT5 NM_138713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138713.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFAT5	NM_138713.4	MANE Select	c.128-11811T>C		intron	N/A	NP_619727.2
	NFAT5	NM_001113178.3		c.128-11811T>C		intron	N/A	NP_001106649.1
	NFAT5	NM_006599.4		c.74-11811T>C		intron	N/A	NP_006590.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFAT5	ENST00000349945.7	TSL:1 MANE Select	c.128-11811T>C		intron	N/A	ENSP00000338806.3
	NFAT5	ENST00000567239.5	TSL:1	c.128-11811T>C		intron	N/A	ENSP00000457593.1
	NFAT5	ENST00000354436.6	TSL:1	c.74-11811T>C		intron	N/A	ENSP00000346420.2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33341 AN: 152038 Hom.: 3965 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.219 AC: 33374 AN: 152158 Hom.: 3972 Cov.: 31 AF XY: 0.226 AC XY: 16781 AN XY: 74394

African (AFR) AF: 0.188 AC: 7799 AN: 41514

American (AMR) AF: 0.329 AC: 5029 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 619 AN: 3470

East Asian (EAS) AF: 0.451 AC: 2335 AN: 5172

South Asian (SAS) AF: 0.337 AC: 1625 AN: 4822

European-Finnish (FIN) AF: 0.190 AC: 2014 AN: 10596

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

European-Non Finnish (NFE) AF: 0.194 AC: 13189 AN: 67986

Other (OTH) AF: 0.240 AC: 506 AN: 2110

Alfa AF: 0.164 Hom.: 543

Bravo AF: 0.230

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.5
DANN	Benign	0.66
PhyloP100		0.012
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: rs7198242; hg19: chr16-69648495;