NM_003405.4:c.87+1151A>G

Variant names:

• chr22-31945971-A-G
• rs7291050
• NM_003405.4:c.87+1151A>G

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+1151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,138 control chromosomes in the GnomAD database, including 3,118 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 0.18 (3118 hom., cov: 32)
• Consequence: YWHAH NM_003405.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAH	NM_003405.4	c.87+1151A>G		intron_variant	Intron 1 of 1	ENST00000248975.6	NP_003396.1
LOC124900477	XR_007068065.1	n.581+293A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAH	ENST00000248975.6	c.87+1151A>G		intron_variant	Intron 1 of 1	1	NM_003405.4	ENSP00000248975.5
ENSG00000285404	ENST00000646701.1	c.1787-10168A>G		intron_variant	Intron 20 of 20			ENSP00000496158.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27708 AN: 152020 Hom.: 3115 Cov.: 32

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.182 AC: 27719 AN: 152138 Hom.: 3118 Cov.: 32 AF XY: 0.185 AC XY: 13774 AN XY: 74382

African (AFR) AF: 0.0569 AC: 2365 AN: 41532

American (AMR) AF: 0.173 AC: 2651 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3470

East Asian (EAS) AF: 0.115 AC: 598 AN: 5182

South Asian (SAS) AF: 0.232 AC: 1117 AN: 4818

European-Finnish (FIN) AF: 0.266 AC: 2818 AN: 10576

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16667 AN: 67964

Other (OTH) AF: 0.179 AC: 378 AN: 2108

Alfa AF: 0.231 Hom.: 2235

Bravo AF: 0.166

Asia WGS AF: 0.150 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.65
PhyloP100		-0.56
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: rs7291050; hg19: chr22-32341957;