16-69696523-A-G

Variant names:

• chr16-69696523-A-G
• rs1437134
• ENST00000393742.7:n.*4584A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000393742.7(NFAT5):​n.*4584A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,482 control chromosomes in the GnomAD database, including 33,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33617 hom., cov: 32)
  • Exomes 𝑓: 0.59 (77 hom.)
• Consequence: NFAT5 ENST00000393742.7 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.534
• Publications: 20 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 16-69696523-A-G is Benign according to our data. Variant chr16-69696523-A-G is described in ClinVar as Benign. ClinVar VariationId is 1227923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAT5	NM_138713.4	c.*172A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000349945.7	NP_619727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAT5	ENST00000349945.7	c.*172A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_138713.4	ENSP00000338806.3

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99848 AN: 151932 Hom.: 33563 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.651

GnomAD4 exome AF: 0.590 AC: 255 AN: 432 Hom.: 77 Cov.: 0 AF XY: 0.596 AC XY: 155 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.587 AC: 250 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.657 AC: 99972 AN: 152050 Hom.: 33617 Cov.: 32 AF XY: 0.658 AC XY: 48927 AN XY: 74326

African (AFR) AF: 0.783 AC: 32497 AN: 41486

American (AMR) AF: 0.653 AC: 9966 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1983 AN: 3468

East Asian (EAS) AF: 0.886 AC: 4589 AN: 5182

South Asian (SAS) AF: 0.688 AC: 3314 AN: 4818

European-Finnish (FIN) AF: 0.568 AC: 6007 AN: 10570

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39487 AN: 67952

Other (OTH) AF: 0.653 AC: 1372 AN: 2102

Alfa AF: 0.607 Hom.: 32804

Bravo AF: 0.672

Asia WGS AF: 0.731 AC: 2533 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26506053)

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
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: rs1437134; hg19: chr16-69730426;