7-76356056-A-G

Variant names:

• chr7-76356056-A-G
• rs11765693
• NM_012479.4:c.87+2666T>C

Variant summary

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

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]

YWHAG Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 56

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012479.4. 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
	YWHAG	NM_012479.4	MANE Select	c.87+2666T>C		intron	N/A	NP_036611.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAG	ENST00000307630.5	TSL:1 MANE Select	c.87+2666T>C		intron	N/A	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

African (AFR) AF: 0.315 AC: 13051 AN: 41488

American (AMR) AF: 0.285 AC: 4358 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 695 AN: 3468

East Asian (EAS) AF: 0.442 AC: 2287 AN: 5178

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4828

European-Finnish (FIN) AF: 0.364 AC: 3845 AN: 10560

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.285 AC: 19413 AN: 68002

Other (OTH) AF: 0.283 AC: 597 AN: 2112

Alfa AF: 0.294 Hom.: 2136

Bravo AF: 0.301

Asia WGS AF: 0.346 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.36
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11765693; hg19: chr7-75985373;