rs3752826

chr17-1361770-A-Cchr17-1361770-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006761.5(YWHAE):c.371+132T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 590,130 control chromosomes in the GnomAD database, including 138,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.74 (42822 hom., cov: 32)
  • Exomes 𝑓: 0.66 (95510 hom.)
• Consequence: YWHAE NM_006761.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.355

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 17-1361770-A-C is Benign according to our data. Variant chr17-1361770-A-C is described in ClinVar as [Benign]. Clinvar id is 1258946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAE	NM_006761.5	c.371+132T>G		intron_variant		ENST00000264335.13
YWHAE	NR_024058.2	n.516+132T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAE	ENST00000264335.13	c.371+132T>G		intron_variant		1	NM_006761.5	P1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112101 AN: 151988 Hom.: 42751 Cov.: 32

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.723

GnomAD4 exome AF: 0.657 AC: 287753 AN: 438024 Hom.: 95510 Cov.: 6 AF XY: 0.655 AC XY: 148102 AN XY: 226148

Gnomad4 AFR exome AF: 0.929

Gnomad4 AMR exome AF: 0.797

Gnomad4 ASJ exome AF: 0.670

Gnomad4 EAS exome AF: 0.527

Gnomad4 SAS exome AF: 0.650

Gnomad4 FIN exome AF: 0.665

Gnomad4 NFE exome AF: 0.651

Gnomad4 OTH exome AF: 0.672

GnomAD4 genome AF: 0.738 AC: 112237 AN: 152106 Hom.: 42822 Cov.: 32 AF XY: 0.734 AC XY: 54573 AN XY: 74364

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.724

Alfa AF: 0.722 Hom.: 5928

Bravo AF: 0.754

Asia WGS AF: 0.622 AC: 2163 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.95
Dann	Benign	0.37

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: rs3752826; hg19: chr17-1265064;