rs4820059

Positions:

• chr22-31950481-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003405.4(YWHAH):​c.88-5658G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 762,482 control chromosomes in the GnomAD database, including 46,763 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 0.28 (7598 hom., cov: 30)
  • Exomes 𝑓: 0.35 (39165 hom.)
• Consequence: YWHAH NM_003405.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393

Genes affected

YWHAH (HGNC:12853): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta) 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 99% identical to the mouse, rat and bovine orthologs. This gene contains a 7 bp repeat sequence in its 5' UTR, and changes in the number of this repeat have been associated with early-onset schizophrenia and psychotic bipolar disorder. [provided by RefSeq, Jun 2009]

ENSG00000285404 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YWHAH	NM_003405.4	c.88-5658G>A		intron_variant		ENST00000248975.6	NP_003396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YWHAH	ENST00000248975.6	c.88-5658G>A		intron_variant		1	NM_003405.4	ENSP00000248975.5
ENSG00000285404	ENST00000646701.1	c.1787-5658G>A		intron_variant				ENSP00000496158.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43207 AN: 151756 Hom.: 7591 Cov.: 30

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.347 AC: 212184 AN: 610608 Hom.: 39165 AF XY: 0.349 AC XY: 115845 AN XY: 332350

Gnomad4 AFR exome AF: 0.0834

Gnomad4 AMR exome AF: 0.370

Gnomad4 ASJ exome AF: 0.366

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.285 AC: 43228 AN: 151874 Hom.: 7598 Cov.: 30 AF XY: 0.285 AC XY: 21161 AN XY: 74202

Gnomad4 AFR AF: 0.0840

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.295

Alfa AF: 0.361 Hom.: 4902

Bravo AF: 0.273

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.69

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: rs4820059; hg19: chr22-32346468; COSMIC: COSV50708307; COSMIC: COSV50708307;