rs3747158

Positions:

• chr22-31946989-G-A

Variant summary

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

The ENST00000248975.6(YWHAH):​c.87+2169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 151,978 control chromosomes in the GnomAD database, including 13,386 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 0.42 (13386 hom., cov: 32)
• Consequence: YWHAH ENST00000248975.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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]

LOC124900477 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YWHAH	NM_003405.4	c.87+2169G>A		intron_variant		ENST00000248975.6	NP_003396.1
LOC124900477	XR_007068065.1	n.582-475G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YWHAH	ENST00000248975.6	c.87+2169G>A		intron_variant		1	NM_003405.4	ENSP00000248975	P1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62972 AN: 151860 Hom.: 13346 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.415 AC: 63072 AN: 151978 Hom.: 13386 Cov.: 32 AF XY: 0.412 AC XY: 30595 AN XY: 74286

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.388

Alfa AF: 0.402 Hom.: 11508

Bravo AF: 0.419

Asia WGS AF: 0.320 AC: 1113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.16

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: rs3747158; hg19: chr22-32342976;