rs2239535

Positions:

• chr20-44887515-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139323.4(YWHAB):​c.-4+1629G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,084 control chromosomes in the GnomAD database, including 7,867 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.30 (7867 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: YWHAB NM_139323.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YWHAB	NM_139323.4	c.-4+1629G>A		intron_variant		ENST00000353703.9	NP_647539.1
YWHAB	NM_003404.5	c.-98-133G>A		intron_variant			NP_003395.1
YWHAB	XM_017028040.2	c.-4+1629G>A		intron_variant			XP_016883529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YWHAB	ENST00000353703.9	c.-4+1629G>A		intron_variant		1	NM_139323.4	ENSP00000300161.4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45168 AN: 151960 Hom.: 7852 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.297 AC: 45233 AN: 152078 Hom.: 7867 Cov.: 32 AF XY: 0.291 AC XY: 21632 AN XY: 74354

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.304

Alfa AF: 0.251 Hom.: 8521

Bravo AF: 0.306

Asia WGS AF: 0.203 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.056
DANN	Benign	0.68
BranchPoint Hunter		0.0

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

LitVar

Other links and lift over

dbSNP: rs2239535; hg19: chr20-43516156;