rs28365859

Variant names:

• chr17-1400484-C-G
• rs28365859
• ENST00000928923.1:c.-374G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000928923.1(YWHAE):​c.-374G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 353,948 control chromosomes in the GnomAD database, including 23,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11210 hom., cov: 33)
  • Exomes 𝑓: 0.34 (11912 hom.)
• Consequence: YWHAE ENST00000928923.1 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.241
• Publications: 12 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 17-1400484-C-G is Benign according to our data. Variant chr17-1400484-C-G is described in ClinVar as Benign. ClinVar VariationId is 1269387.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000928923.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAE	ENST00000928923.1		c.-374G>C		upstream_gene	N/A	ENSP00000598982.1
	YWHAE	ENST00000928924.1		c.-374G>C		upstream_gene	N/A	ENSP00000598983.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57263 AN: 152092 Hom.: 11173 Cov.: 33

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.338 AC: 68271 AN: 201738 Hom.: 11912 AF XY: 0.344 AC XY: 35415 AN XY: 102844

African (AFR) AF: 0.473 AC: 2760 AN: 5840

American (AMR) AF: 0.338 AC: 2294 AN: 6786

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 2857 AN: 7738

East Asian (EAS) AF: 0.239 AC: 3534 AN: 14768

South Asian (SAS) AF: 0.462 AC: 8149 AN: 17644

European-Finnish (FIN) AF: 0.341 AC: 3296 AN: 9672

Middle Eastern (MID) AF: 0.327 AC: 322 AN: 986

European-Non Finnish (NFE) AF: 0.324 AC: 40539 AN: 125034

Other (OTH) AF: 0.341 AC: 4520 AN: 13270

GnomAD4 genome AF: 0.377 AC: 57369 AN: 152210 Hom.: 11210 Cov.: 33 AF XY: 0.378 AC XY: 28131 AN XY: 74434

African (AFR) AF: 0.479 AC: 19913 AN: 41532

American (AMR) AF: 0.359 AC: 5485 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1373 AN: 5182

South Asian (SAS) AF: 0.461 AC: 2224 AN: 4828

European-Finnish (FIN) AF: 0.343 AC: 3636 AN: 10596

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22398 AN: 67984

Other (OTH) AF: 0.349 AC: 738 AN: 2116

Alfa AF: 0.363 Hom.: 1333

Bravo AF: 0.377

Asia WGS AF: 0.386 AC: 1342 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.3
DANN	Benign	0.81
PhyloP100		0.24
PromoterAI		0.069	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs28365859; hg19: chr17-1303778;