rs16945811

Variant names:

• chr17-1391320-G-A
• rs16945811
• NM_006761.5:c.64+8727C>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.64+8727C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0711 in 152,106 control chromosomes in the GnomAD database, including 439 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 0.071 (439 hom., cov: 32)
• Consequence: YWHAE NM_006761.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAE	NM_006761.5	c.64+8727C>T		intron_variant	Intron 1 of 5	ENST00000264335.13	NP_006752.1
YWHAE	NR_024058.2	n.176+8727C>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAE	ENST00000264335.13	c.64+8727C>T		intron_variant	Intron 1 of 5	1	NM_006761.5	ENSP00000264335.8

Frequencies

GnomAD3 genomes AF: 0.0711 AC: 10808 AN: 151988 Hom.: 438 Cov.: 32

Gnomad AFR AF: 0.0905

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0566

Gnomad FIN AF: 0.0364

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0704

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0711 AC: 10818 AN: 152106 Hom.: 439 Cov.: 32 AF XY: 0.0677 AC XY: 5038 AN XY: 74362

African (AFR) AF: 0.0906 AC: 3758 AN: 41486

American (AMR) AF: 0.0653 AC: 998 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5180

South Asian (SAS) AF: 0.0569 AC: 274 AN: 4818

European-Finnish (FIN) AF: 0.0364 AC: 385 AN: 10580

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0704 AC: 4784 AN: 67978

Other (OTH) AF: 0.0719 AC: 152 AN: 2114

Alfa AF: 0.0681 Hom.: 64

Bravo AF: 0.0743

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		-0.48
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: rs16945811; hg19: chr17-1294614;