rs4790084

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
YWHAE	NM_006761.5	c.65-14627T>C		intron_variant		ENST00000264335.13	NP_006752.1
YWHAE	NR_024058.2	n.177-9944T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YWHAE	ENST00000264335.13	c.65-14627T>C		intron_variant		1	NM_006761.5	ENSP00000264335	P1

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

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.487

Alfa AF: 0.401 Hom.: 25672

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4790084; hg19: chr17-1282979;