rs6734469

chr2-9595771-G-A

Variant summary

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

The NM_006826.4(YWHAQ):c.295-4256C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 150,632 control chromosomes in the GnomAD database, including 27,849 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 0.58 (27849 hom., cov: 27)
• Consequence: YWHAQ NM_006826.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472

Genes affected

YWHAQ (HGNC:12854): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta) 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 and rat orthologs. This gene is upregulated in patients with amyotrophic lateral sclerosis. It contains in its 5' UTR a 6 bp tandem repeat sequence which is polymorphic, however, there is no correlation between the repeat number and the disease. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAQ	NM_006826.4	c.295-4256C>T		intron_variant		ENST00000238081.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAQ	ENST00000238081.8	c.295-4256C>T		intron_variant		1	NM_006826.4	P1
YWHAQ	ENST00000381844.8	c.295-4256C>T		intron_variant		1		P1
YWHAQ	ENST00000446619.1	c.295-4256C>T		intron_variant		3
YWHAQ	ENST00000474715.1	n.61-4256C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.582 AC: 87608 AN: 150526 Hom.: 27813 Cov.: 27

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.582 AC: 87695 AN: 150632 Hom.: 27849 Cov.: 27 AF XY: 0.571 AC XY: 41912 AN XY: 73416

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.0607

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.593

Alfa AF: 0.353 Hom.: 748

Bravo AF: 0.585

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.037
Dann	Benign	0.61

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: rs6734469; hg19: chr2-9735900;