rs17149177

Positions:

• chr7-76356235-G-A

Variant summary

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

The NM_012479.4(YWHAG):​c.87+2487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,120 control chromosomes in the GnomAD database, including 2,840 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 0.17 (2840 hom., cov: 33)
• Consequence: YWHAG NM_012479.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YWHAG	NM_012479.4	c.87+2487C>T		intron_variant		ENST00000307630.5	NP_036611.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YWHAG	ENST00000307630.5	c.87+2487C>T		intron_variant		1	NM_012479.4	ENSP00000306330.3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26596 AN: 152004 Hom.: 2838 Cov.: 33

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.175 AC: 26598 AN: 152120 Hom.: 2840 Cov.: 33 AF XY: 0.177 AC XY: 13141 AN XY: 74346

Gnomad4 AFR AF: 0.0646

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.181

Alfa AF: 0.201 Hom.: 3275

Bravo AF: 0.174

Asia WGS AF: 0.280 AC: 968 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.65

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: rs17149177; hg19: chr7-75985552;