7-76346269-C-T

Variant names:

• chr7-76346269-C-T
• rs7779014
• NM_012479.4:c.87+12453G>A

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+12453G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,046 control chromosomes in the GnomAD database, including 6,982 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 (6982 hom., cov: 32)
• Consequence: YWHAG NM_012479.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 18 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: Ambry Genetics, Illumina, 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAG	NM_012479.4	MANE Select	c.87+12453G>A		intron	N/A	NP_036611.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAG	ENST00000307630.5	TSL:1 MANE Select	c.87+12453G>A		intron	N/A	ENSP00000306330.3	P61981

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45472 AN: 151928 Hom.: 6976 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.299 AC: 45487 AN: 152046 Hom.: 6982 Cov.: 32 AF XY: 0.303 AC XY: 22520 AN XY: 74308

African (AFR) AF: 0.314 AC: 13005 AN: 41450

American (AMR) AF: 0.285 AC: 4362 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 695 AN: 3472

East Asian (EAS) AF: 0.440 AC: 2268 AN: 5150

South Asian (SAS) AF: 0.209 AC: 1009 AN: 4830

European-Finnish (FIN) AF: 0.364 AC: 3842 AN: 10558

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.285 AC: 19401 AN: 67992

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

Alfa AF: 0.286 Hom.: 12278

Bravo AF: 0.301

Asia WGS AF: 0.343 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.81
DANN	Benign	0.88
PhyloP100		-0.32
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: rs7779014; hg19: chr7-75975586;