rs6734469

Variant names:

• chr2-9595771-G-A
• rs6734469
• NM_006826.4:c.295-4256C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006826.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAQ	NM_006826.4	MANE Select	c.295-4256C>T		intron	N/A	NP_006817.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAQ	ENST00000238081.8	TSL:1 MANE Select	c.295-4256C>T		intron	N/A	ENSP00000238081.3
	YWHAQ	ENST00000381844.8	TSL:1	c.295-4256C>T		intron	N/A	ENSP00000371267.4
	YWHAQ	ENST00000446619.1	TSL:3	c.295-4256C>T		intron	N/A	ENSP00000398990.1

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

African (AFR) AF: 0.810 AC: 33106 AN: 40896

American (AMR) AF: 0.427 AC: 6435 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2200 AN: 3466

East Asian (EAS) AF: 0.0607 AC: 312 AN: 5144

South Asian (SAS) AF: 0.380 AC: 1817 AN: 4784

European-Finnish (FIN) AF: 0.513 AC: 5200 AN: 10138

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36724 AN: 67858

Other (OTH) AF: 0.593 AC: 1239 AN: 2090

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.037
DANN	Benign	0.61
PhyloP100		-0.47
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: rs6734469; hg19: chr2-9735900;