rs3752826

Variant names:

• chr17-1361770-A-C
• rs3752826
• NM_006761.5:c.371+132T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-1361770-A-C
• chr17-1361770-A-G
• chr17-1361770-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.355
• 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 -20 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 VariationId is 1258946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006761.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAE	NM_006761.5	MANE Select	c.371+132T>G		intron	N/A	NP_006752.1
	YWHAE	NR_024058.2		n.516+132T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAE	ENST00000264335.13	TSL:1 MANE Select	c.371+132T>G		intron	N/A	ENSP00000264335.8
	YWHAE	ENST00000571732.5	TSL:1	c.305+132T>G		intron	N/A	ENSP00000461762.1
	YWHAE	ENST00000469398.5	TSL:2	n.577T>G		non_coding_transcript_exon	Exon 4 of 4

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

African (AFR) AF: 0.929 AC: 10019 AN: 10782

American (AMR) AF: 0.797 AC: 9342 AN: 11716

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 7989 AN: 11930

East Asian (EAS) AF: 0.527 AC: 14454 AN: 27402

South Asian (SAS) AF: 0.650 AC: 17319 AN: 26644

European-Finnish (FIN) AF: 0.665 AC: 27256 AN: 40960

Middle Eastern (MID) AF: 0.575 AC: 1017 AN: 1768

European-Non Finnish (NFE) AF: 0.651 AC: 184525 AN: 283278

Other (OTH) AF: 0.672 AC: 15832 AN: 23544

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

African (AFR) AF: 0.929 AC: 38586 AN: 41526

American (AMR) AF: 0.791 AC: 12077 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2343 AN: 3472

East Asian (EAS) AF: 0.472 AC: 2443 AN: 5174

South Asian (SAS) AF: 0.652 AC: 3148 AN: 4828

European-Finnish (FIN) AF: 0.657 AC: 6928 AN: 10544

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44430 AN: 67990

Other (OTH) AF: 0.724 AC: 1527 AN: 2108

Alfa AF: 0.729 Hom.: 6258

Bravo AF: 0.754

Asia WGS AF: 0.622 AC: 2163 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.95
DANN	Benign	0.37
PhyloP100		-0.35
PromoterAI		0.013	Neutral
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: rs3752826; hg19: chr17-1265064;