Variant chr20-44901841-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_139323.4(YWHAB):c.300+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000537 in 1,585,796 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

YWHAB
NM_139323.4 splice_region, intron

Scores

Splicing: ADA: 0.0001705

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.271

Variant links:

Genes affected

YWHAB (HGNC:12849): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta) This gene encodes a protein belonging to the 14-3-3 family of proteins, members of which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals. The encoded protein has been shown to interact with RAF1 and CDC25 phosphatases, suggesting that it may play a role in linking mitogenic signaling and the cell cycle machinery. Two transcript variants, which encode the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]

YWHAB links:

YWHAB (HGNC:):

YWHAB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 20-44901841-G-A is Benign according to our data. Variant chr20-44901841-G-A is described in ClinVar as [Benign]. Clinvar id is 719598.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 468 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
YWHAB	NM_139323.4 linkuse as main transcript	c.300+8G>A	splice_region_variant, intron_variant	ENST00000353703.9	NP_647539.1	P31946-1V9HWD6
YWHAB	NM_003404.5 linkuse as main transcript	c.300+8G>A	splice_region_variant, intron_variant		NP_003395.1	P31946-1V9HWD6
YWHAB	XM_017028040.2 linkuse as main transcript	c.300+8G>A	splice_region_variant, intron_variant		XP_016883529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YWHAB	ENST00000353703.9 linkuse as main transcript	c.300+8G>A		splice_region_variant, intron_variant		1	NM_139323.4	ENSP00000300161.4		P31946-1

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

465

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000666

AC:

161

AN:

241752

Hom.:

AF XY:

0.000490

AC XY:

AN XY:

130498

show subpopulations

Gnomad AFR exome

AF:

0.00943

Gnomad AMR exome

AF:

0.000150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.000267

AC:

383

AN:

1433494

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

160

AN XY:

708086

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.000115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000641

Gnomad4 OTH exome

AF:

0.000543

GnomAD4 genome

AF:

0.00307

AC:

468

AN:

152302

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

232

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00268

Hom.:

Bravo

AF:

0.00317

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.3

DANN

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.0080

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over