rs933226

Variant names:

• chr22-31947860-T-C
• rs933226
• NM_003405.4:c.87+3040T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003405.4(YWHAH):​c.87+3040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,222 control chromosomes in the GnomAD database, including 1,738 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 0.14 (1738 hom., cov: 33)
• Consequence: YWHAH NM_003405.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAH	NM_003405.4	c.87+3040T>C		intron_variant	Intron 1 of 1	ENST00000248975.6	NP_003396.1
LOC124900477	XR_007068065.1	n.978T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAH	ENST00000248975.6	c.87+3040T>C		intron_variant	Intron 1 of 1	1	NM_003405.4	ENSP00000248975.5
ENSG00000285404	ENST00000646701.1	c.1787-8279T>C		intron_variant	Intron 20 of 20			ENSP00000496158.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20659 AN: 152104 Hom.: 1736 Cov.: 33

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.136 AC: 20662 AN: 152222 Hom.: 1738 Cov.: 33 AF XY: 0.137 AC XY: 10226 AN XY: 74424

African (AFR) AF: 0.0422 AC: 1752 AN: 41564

American (AMR) AF: 0.127 AC: 1950 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3468

East Asian (EAS) AF: 0.0907 AC: 470 AN: 5184

South Asian (SAS) AF: 0.152 AC: 735 AN: 4828

European-Finnish (FIN) AF: 0.200 AC: 2112 AN: 10572

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12563 AN: 67996

Other (OTH) AF: 0.124 AC: 261 AN: 2108

Alfa AF: 0.149 Hom.: 327

Bravo AF: 0.124

Asia WGS AF: 0.105 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.8
DANN	Benign	0.82
PhyloP100		0.43
PromoterAI		-0.00070	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: rs933226; hg19: chr22-32343847;