rs61730074

Variant names:

• chr16-69692351-G-A
• rs61730074
• NM_138713.4:c.2526G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_138713.4(NFAT5):​c.2526G>A​(p.Glu842Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00982 in 1,614,198 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (16 hom., cov: 32)
  • Exomes 𝑓: 0.010 (99 hom.)
• Consequence: NFAT5 NM_138713.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.740
• Publications: 7 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 16-69692351-G-A is Benign according to our data. Variant chr16-69692351-G-A is described in ClinVar as Benign. ClinVar VariationId is 456656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.74 with no splicing effect.
• BS2: High AC in GnomAd4 at 1203 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.2526G>A	p.Glu842Glu	synonymous_variant	Exon 13 of 15	ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7	c.2526G>A	p.Glu842Glu	synonymous_variant	Exon 13 of 15	1	NM_138713.4	ENSP00000338806.3

Frequencies

GnomAD3 genomes AF: 0.00790 AC: 1202 AN: 152188 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00594

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00859 AC: 2160 AN: 251352 AF XY: 0.00876

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00590

Gnomad ASJ exome AF: 0.0181

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00799

Gnomad NFE exome AF: 0.0123

Gnomad OTH exome AF: 0.00896

GnomAD4 exome AF: 0.0100 AC: 14650 AN: 1461892 Hom.: 99 Cov.: 32 AF XY: 0.00996 AC XY: 7245 AN XY: 727248

African (AFR) AF: 0.00108 AC: 36 AN: 33480

American (AMR) AF: 0.00619 AC: 277 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 469 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00457 AC: 394 AN: 86258

European-Finnish (FIN) AF: 0.00702 AC: 375 AN: 53420

Middle Eastern (MID) AF: 0.00954 AC: 55 AN: 5768

European-Non Finnish (NFE) AF: 0.0112 AC: 12482 AN: 1112010

Other (OTH) AF: 0.00929 AC: 561 AN: 60396

GnomAD4 genome AF: 0.00790 AC: 1203 AN: 152306 Hom.: 16 Cov.: 32 AF XY: 0.00761 AC XY: 567 AN XY: 74476

African (AFR) AF: 0.00156 AC: 65 AN: 41574

American (AMR) AF: 0.0120 AC: 183 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4828

European-Finnish (FIN) AF: 0.00594 AC: 63 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0109 AC: 741 AN: 68028

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00957 Hom.: 13

Bravo AF: 0.00801

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NFAT5: BP4, BP7, BS1, BS2 -

NFAT5-related disorder Benign:1

Jul 03, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Immunodeficiency Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.1
DANN	Benign	0.66
PhyloP100		0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=78/22	polymorphism

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: rs61730074; hg19: chr16-69726254;