Variant rs34137556 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000264335.13(YWHAE):c.282G>A(p.Lys94=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,585,946 control chromosomes in the GnomAD database, including 824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 48 hom., cov: 31)

Exomes 𝑓: 0.030 ( 776 hom. )

Consequence

YWHAE
ENST00000264335.13 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.193

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 17-1361991-C-T is Benign according to our data. Variant chr17-1361991-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-1361991-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.193 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.023 (3481/151374) while in subpopulation NFE AF= 0.0348 (2365/67966). AF 95% confidence interval is 0.0336. There are 48 homozygotes in gnomad4. There are 1596 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3481 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YWHAE	NM_006761.5 linkuse as main transcript	c.282G>A	p.Lys94=	synonymous_variant	3/6	ENST00000264335.13	NP_006752.1
YWHAE	NR_024058.2 linkuse as main transcript	n.427G>A		non_coding_transcript_exon_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YWHAE	ENST00000264335.13 linkuse as main transcript	c.282G>A	p.Lys94=	synonymous_variant	3/6	1	NM_006761.5	ENSP00000264335	P1	P62258-1

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3483

AN:

151256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00662

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0305

Gnomad FIN

AF:

0.0178

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0348

Gnomad OTH

AF:

0.0208

GnomAD3 exomes

AF:

0.0237

AC:

5358

AN:

225938

Hom.:

AF XY:

0.0254

AC XY:

3132

AN XY:

123232

show subpopulations

Gnomad AFR exome

AF:

0.00533

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.0244

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0331

Gnomad FIN exome

AF:

0.0148

Gnomad NFE exome

AF:

0.0319

Gnomad OTH exome

AF:

0.0259

GnomAD4 exome

AF:

0.0302

AC:

43357

AN:

1434572

Hom.:

776

Cov.:

AF XY:

0.0309

AC XY:

22031

AN XY:

713542

show subpopulations

Gnomad4 AFR exome

AF:

0.00474

Gnomad4 AMR exome

AF:

0.0139

Gnomad4 ASJ exome

AF:

0.0240

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0346

Gnomad4 FIN exome

AF:

0.0165

Gnomad4 NFE exome

AF:

0.0332

Gnomad4 OTH exome

AF:

0.0268

GnomAD4 genome

AF:

0.0230

AC:

3481

AN:

151374

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1596

AN XY:

74028

show subpopulations

Gnomad4 AFR

AF:

0.00660

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.0239

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0301

Gnomad4 FIN

AF:

0.0178

Gnomad4 NFE

AF:

0.0348

Gnomad4 OTH

AF:

0.0205

Alfa

AF:

0.0285

Hom.:

Bravo

AF:

0.0216

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

8.2

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over