chr7-76356056-A-G

Position:

• chr7-76356056-A-G

Variant summary

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

The NM_012479.4(YWHAG):​c.87+2666T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,104 control chromosomes in the GnomAD database, including 7,020 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 0.30 (7020 hom., cov: 33)
• Consequence: YWHAG NM_012479.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YWHAG	NM_012479.4	c.87+2666T>C		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+2666T>C		intron_variant		1	NM_012479.4	ENSP00000306330.3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45549 AN: 151986 Hom.: 7014 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.300 AC: 45564 AN: 152104 Hom.: 7020 Cov.: 33 AF XY: 0.303 AC XY: 22550 AN XY: 74336

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.283

Alfa AF: 0.281 Hom.: 947

Bravo AF: 0.301

Asia WGS AF: 0.346 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11765693; hg19: chr7-75985373;