17-1380704-T-C

Variant names:

• chr17-1380704-T-C
• rs11655548
• NM_006761.5:c.65-15646A>G

Variant summary

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

The NM_006761.5(YWHAE):​c.65-15646A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,106 control chromosomes in the GnomAD database, including 8,026 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 0.32 (8026 hom., cov: 32)
• Consequence: YWHAE NM_006761.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAE	NM_006761.5	c.65-15646A>G		intron_variant	Intron 1 of 5	ENST00000264335.13	NP_006752.1
YWHAE	NR_024058.2	n.177-10963A>G		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAE	ENST00000264335.13	c.65-15646A>G		intron_variant	Intron 1 of 5	1	NM_006761.5	ENSP00000264335.8

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48163 AN: 151988 Hom.: 8003 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.317 AC: 48238 AN: 152106 Hom.: 8026 Cov.: 32 AF XY: 0.325 AC XY: 24132 AN XY: 74350

African (AFR) AF: 0.263 AC: 10936 AN: 41520

American (AMR) AF: 0.487 AC: 7433 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3470

East Asian (EAS) AF: 0.318 AC: 1647 AN: 5174

South Asian (SAS) AF: 0.381 AC: 1837 AN: 4818

European-Finnish (FIN) AF: 0.349 AC: 3690 AN: 10568

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20687 AN: 67978

Other (OTH) AF: 0.325 AC: 686 AN: 2112

Alfa AF: 0.310 Hom.: 23352

Bravo AF: 0.324

Asia WGS AF: 0.363 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.77
PhyloP100		-0.44
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: rs11655548; hg19: chr17-1283998;