rs11763069

Positions:

• chr7-76350362-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_012479.4(YWHAG):​c.87+8360C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 152,260 control chromosomes in the GnomAD database, including 46 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 0.021 (46 hom., cov: 32)
• Consequence: YWHAG NM_012479.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

Genes affected

YWHAG (HGNC:12852): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma) 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 100% identical to the rat ortholog. It is induced by growth factors in human vascular smooth muscle cells, and is also highly expressed in skeletal and heart muscles, suggesting an important role for this protein in muscle tissue. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0211 (3218/152260) while in subpopulation NFE AF= 0.0317 (2156/68022). AF 95% confidence interval is 0.0306. There are 46 homozygotes in gnomad4. There are 1540 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3218 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAG	NM_012479.4	c.87+8360C>T		intron_variant		ENST00000307630.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAG	ENST00000307630.5	c.87+8360C>T		intron_variant		1	NM_012479.4	P1

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3217 AN: 152142 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0172

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

GnomAD4 genome AF: 0.0211 AC: 3218 AN: 152260 Hom.: 46 Cov.: 32 AF XY: 0.0207 AC XY: 1540 AN XY: 74432

Gnomad4 AFR AF: 0.00558

Gnomad4 AMR AF: 0.0131

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0315

Gnomad4 NFE AF: 0.0317

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0286 Hom.: 92

Bravo AF: 0.0195

Asia WGS AF: 0.00260 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.75

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: rs11763069; hg19: chr7-75979679;