rs2853884

Positions:

• chr22-31952326-T-C

Variant summary

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

The NM_003405.4(YWHAH):​c.88-3813T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,162 control chromosomes in the GnomAD database, including 5,427 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 0.24 (5427 hom., cov: 32)
• Consequence: YWHAH NM_003405.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YWHAH	NM_003405.4	c.88-3813T>C		intron_variant		ENST00000248975.6	NP_003396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YWHAH	ENST00000248975.6	c.88-3813T>C		intron_variant		1	NM_003405.4	ENSP00000248975	P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36591 AN: 152044 Hom.: 5420 Cov.: 32

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.241 AC: 36608 AN: 152162 Hom.: 5427 Cov.: 32 AF XY: 0.243 AC XY: 18051 AN XY: 74398

Gnomad4 AFR AF: 0.0721

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.257

Alfa AF: 0.281 Hom.: 863

Bravo AF: 0.231

Asia WGS AF: 0.221 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.80

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: rs2853884; hg19: chr22-32348313;