rs4790084

Variant names:

• chr17-1379685-A-G
• rs4790084
• NM_006761.5:c.65-14627T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-1379685-A-G
• chr17-1379685-A-T

Variant summary

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

The NM_006761.5(YWHAE):​c.65-14627T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,948 control chromosomes in the GnomAD database, including 19,805 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 0.49 (19805 hom., cov: 32)
• Consequence: YWHAE NM_006761.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 18 publications found

Genes affected

YWHAE (HGNC:12851): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon) This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the mouse ortholog. It interacts with CDC25 phosphatases, RAF1 and IRS1 proteins, suggesting its role in diverse biochemical activities related to signal transduction, such as cell division and regulation of insulin sensitivity. It has also been implicated in the pathogenesis of small cell lung cancer. Two transcript variants, one protein-coding and the other non-protein-coding, have been found for this gene. [provided by RefSeq, Aug 2008]

YWHAE Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAE	NM_006761.5	c.65-14627T>C		intron_variant	Intron 1 of 5	ENST00000264335.13	NP_006752.1
YWHAE	NR_024058.2	n.177-9944T>C		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAE	ENST00000264335.13	c.65-14627T>C		intron_variant	Intron 1 of 5	1	NM_006761.5	ENSP00000264335.8

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74814 AN: 151830 Hom.: 19781 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.493 AC: 74901 AN: 151948 Hom.: 19805 Cov.: 32 AF XY: 0.494 AC XY: 36689 AN XY: 74250

African (AFR) AF: 0.678 AC: 28092 AN: 41416

American (AMR) AF: 0.593 AC: 9056 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1338 AN: 3466

East Asian (EAS) AF: 0.407 AC: 2102 AN: 5162

South Asian (SAS) AF: 0.479 AC: 2307 AN: 4820

European-Finnish (FIN) AF: 0.391 AC: 4128 AN: 10554

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26394 AN: 67962

Other (OTH) AF: 0.487 AC: 1024 AN: 2104

Alfa AF: 0.422 Hom.: 45609

Bravo AF: 0.514

Asia WGS AF: 0.476 AC: 1659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.6
DANN	Benign	0.26
PhyloP100		1.5
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: rs4790084; hg19: chr17-1282979;