dbSNP rs4820059: YWHAH:c.88-5658G>A (chr22-31950481-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003405.4(YWHAH):c.88-5658G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 762,482 control chromosomes in the GnomAD database, including 46,763 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 0.28 ( 7598 hom., cov: 30)

Exomes 𝑓: 0.35 ( 39165 hom. )

Consequence

YWHAH
NM_003405.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.393

Publications

15 publications found

Variant links:

Genes affected

YWHAH (HGNC:12853): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta) 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 99% identical to the mouse, rat and bovine orthologs. This gene contains a 7 bp repeat sequence in its 5' UTR, and changes in the number of this repeat have been associated with early-onset schizophrenia and psychotic bipolar disorder. [provided by RefSeq, Jun 2009]

YWHAH links:

ENSG00000285404 (HGNC:):

ENSG00000285404 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003405.4. 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
	YWHAH	NM_003405.4	MANE Select	c.88-5658G>A		intron	N/A	NP_003396.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
YWHAH	ENST00000248975.6	TSL:1 MANE Select	c.88-5658G>A	intron	N/A	ENSP00000248975.5
ENSG00000285404	ENST00000646701.1		c.1787-5658G>A	intron	N/A	ENSP00000496158.1
YWHAH	ENST00000946727.1		c.297+59G>A	intron	N/A	ENSP00000616786.1

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43207

AN:

151756

Hom.:

7591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0840

Gnomad AMI

AF:

0.324

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.294

GnomAD4 exome

AF:

0.347

AC:

212184

AN:

610608

Hom.:

39165

AF XY:

0.349

AC XY:

115845

AN XY:

332350

show subpopulations

African (AFR)

AF:

0.0834

AC:

1430

AN:

17150

American (AMR)

AF:

0.370

AC:

15567

AN:

42042

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

7484

AN:

20462

East Asian (EAS)

AF:

0.120

AC:

4287

AN:

35690

South Asian (SAS)

AF:

0.325

AC:

22259

AN:

68504

European-Finnish (FIN)

AF:

0.356

AC:

18262

AN:

51320

Middle Eastern (MID)

AF:

0.329

AC:

1017

AN:

3088

European-Non Finnish (NFE)

AF:

0.385

AC:

130943

AN:

340222

Other (OTH)

AF:

0.340

AC:

10935

AN:

32130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

6603

13205

19808

26410

33013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

728

1456

2184

2912

3640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.285

AC:

43228

AN:

151874

Hom.:

7598

Cov.:

AF XY:

0.285

AC XY:

21161

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.0840

AC:

3480

AN:

41442

American (AMR)

AF:

0.340

AC:

5185

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1303

AN:

3470

East Asian (EAS)

AF:

0.143

AC:

739

AN:

5152

South Asian (SAS)

AF:

0.317

AC:

1523

AN:

4804

European-Finnish (FIN)

AF:

0.353

AC:

3721

AN:

10528

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26275

AN:

67912

Other (OTH)

AF:

0.295

AC:

621

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1457

2914

4370

5827

7284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.360

Hom.:

5459

Bravo

AF:

0.273

Asia WGS

AF:

0.240

AC:

834

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.9

(source)

DANN

Benign

0.69

PhyloP100

0.39

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over