dbSNP rs11763069: YWHAG:c.87+8360C>T (chr7-76350362-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_012479.4(YWHAG):c.87+8360C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 152,260 control chromosomes in the GnomAD database, including 46 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 0.021 ( 46 hom., cov: 32)

Consequence

YWHAG
NM_012479.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0460

Publications

8 publications found

Variant links:

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

YWHAG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0211 (3218/152260) while in subpopulation NFE AF = 0.0317 (2156/68022). AF 95% confidence interval is 0.0306. There are 46 homozygotes in GnomAd4. There are 1540 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3218 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAG	NM_012479.4 link	c.87+8360C>T		intron_variant	Intron 1 of 1	ENST00000307630.5	NP_036611.2	P61981

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAG	ENST00000307630.5 link	c.87+8360C>T		intron_variant	Intron 1 of 1	1	NM_012479.4	ENSP00000306330.3		P61981

Frequencies

GnomAD3 genomes

AF:

0.0211

AC:

3217

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00560

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0315

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0317

Gnomad OTH

AF:

0.0172

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

GnomAD4 genome

AF:

0.0211

AC:

3218

AN:

152260

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1540

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00558

AC:

232

AN:

41554

American (AMR)

AF:

0.0131

AC:

201

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0334

AC:

116

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00373

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0315

AC:

334

AN:

10594

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0317

AC:

2156

AN:

68022

Other (OTH)

AF:

0.0170

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

166

333

499

666

832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0286

Hom.:

109

Bravo

AF:

0.0195

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

(source)

DANN

Benign

0.75

PhyloP100

-0.046

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over