rs2239535

Variant names:

• chr20-44887515-G-A
• rs2239535
• ENST00000631616.1:n.1802G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000631616.1(YWHAB):​n.1802G>A variant causes a non coding transcript exon 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.

• Frequency:
  • Genomes: 𝑓 0.30 (7867 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: YWHAB ENST00000631616.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 23 publications found

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]

ACMG classification

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

• BP4: 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000631616.1. 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
	YWHAB	NM_139323.4	MANE Select	c.-4+1629G>A		intron	N/A	NP_647539.1
	YWHAB	NM_003404.5		c.-98-133G>A		intron	N/A	NP_003395.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAB	ENST00000631616.1	TSL:1	n.1802G>A		non_coding_transcript_exon	Exon 1 of 4
	YWHAB	ENST00000353703.9	TSL:1 MANE Select	c.-4+1629G>A		intron	N/A	ENSP00000300161.4
	YWHAB	ENST00000372839.7	TSL:1	c.-98-133G>A		intron	N/A	ENSP00000361930.3

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.480 AC: 19893 AN: 41440

American (AMR) AF: 0.229 AC: 3499 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1112 AN: 3468

East Asian (EAS) AF: 0.131 AC: 679 AN: 5188

South Asian (SAS) AF: 0.175 AC: 843 AN: 4818

European-Finnish (FIN) AF: 0.196 AC: 2072 AN: 10582

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16125 AN: 67978

Other (OTH) AF: 0.304 AC: 642 AN: 2110

Alfa AF: 0.256 Hom.: 21071

Bravo AF: 0.306

Asia WGS AF: 0.203 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.056
DANN	Benign	0.68
PhyloP100		-1.5
BranchPoint Hunter		0.0
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: rs2239535; hg19: chr20-43516156;