rs4669402

Variant names:

• chr2-9639284-G-C
• rs4669402
• ENST00000478468.1:n.150+363G>C

Variant summary

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

The ENST00000862425.1(YWHAQ):​c.-83+77C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 152,338 control chromosomes in the GnomAD database, including 486 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 0.076 (486 hom., cov: 32)
• Consequence: YWHAQ ENST00000862425.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 2 publications found

Genes affected

ENSG00000240687 (HGNC:):

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000862425.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC105373418	NR_187862.1		n.380+30G>C		intron	N/A
	LOC105373418	NR_187863.1		n.177+363G>C		intron	N/A
	LOC105373418	NR_187864.1		n.380+30G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000240687	ENST00000478468.1	TSL:1	n.150+363G>C		intron	N/A
	YWHAQ	ENST00000862425.1		c.-83+77C>G		intron	N/A	ENSP00000532484.1
	ENSG00000240687	ENST00000655108.2		n.463G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0762 AC: 11600 AN: 152220 Hom.: 483 Cov.: 32

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0616

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.0726

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0762 AC: 11613 AN: 152338 Hom.: 486 Cov.: 32 AF XY: 0.0801 AC XY: 5971 AN XY: 74498

African (AFR) AF: 0.0716 AC: 2976 AN: 41584

American (AMR) AF: 0.0615 AC: 941 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0553 AC: 192 AN: 3472

East Asian (EAS) AF: 0.170 AC: 879 AN: 5182

South Asian (SAS) AF: 0.0723 AC: 349 AN: 4830

European-Finnish (FIN) AF: 0.140 AC: 1482 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0671 AC: 4564 AN: 68030

Other (OTH) AF: 0.0747 AC: 158 AN: 2114

Alfa AF: 0.0709 Hom.: 41

Bravo AF: 0.0704

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.39
PhyloP100		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4669402;

hg19: chr2-9779413;