chr7-76355215-G-A

Variant names:

• chr7-76355215-G-A
• rs917424
• NM_012479.4:c.87+3507C>T

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+3507C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,076 control chromosomes in the GnomAD database, including 3,432 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 0.21 (3432 hom., cov: 33)
• Consequence: YWHAG NM_012479.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 12 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAG	NM_012479.4	c.87+3507C>T		intron_variant	Intron 1 of 1	ENST00000307630.5	NP_036611.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAG	ENST00000307630.5	c.87+3507C>T		intron_variant	Intron 1 of 1	1	NM_012479.4	ENSP00000306330.3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31185 AN: 151958 Hom.: 3430 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.205 AC: 31195 AN: 152076 Hom.: 3432 Cov.: 33 AF XY: 0.207 AC XY: 15371 AN XY: 74314

African (AFR) AF: 0.165 AC: 6861 AN: 41512

American (AMR) AF: 0.252 AC: 3847 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3470

East Asian (EAS) AF: 0.330 AC: 1710 AN: 5176

South Asian (SAS) AF: 0.275 AC: 1325 AN: 4814

European-Finnish (FIN) AF: 0.184 AC: 1934 AN: 10534

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14015 AN: 67986

Other (OTH) AF: 0.202 AC: 426 AN: 2110

Alfa AF: 0.204 Hom.: 9266

Bravo AF: 0.207

Asia WGS AF: 0.299 AC: 1036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.66
DANN	Benign	0.74
PhyloP100		-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: rs917424; hg19: chr7-75984532;