rs4318932

Positions:

• chr7-72578056-C-A

Variant summary

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

The ENST00000620995.5(TYW1B):​c.1786-2337G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,228 control chromosomes in the GnomAD database, including 17,445 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 0.45 (17445 hom., cov: 30)
• Consequence: TYW1B ENST00000620995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

Genes affected

TYW1B (HGNC:33908): (tRNA-yW synthesizing protein 1 homolog B) Wybutosine is a hypermodified guanosine found in phenylalanine tRNA. Wybutosine functions to stabilize codon-anticodon interactions during ribosome decoding and therefore supports the maintenance of the reading frame. In yeast, the homolog of this gene is essential for the synthesis of wybutosine. The human genome contains two closely related genes that putatively function in wybutosine synthesis. The open reading frame of this locus is disrupted in some individuals. Thus, this locus appears to be an evolving pseudogene, but may still be functional in some members of the population. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYW1B	NM_001145440.3	c.1786-2337G>T		intron_variant		ENST00000620995.5	NP_001138912.2
TYW1B	NM_001412179.1	c.1558-2337G>T		intron_variant			NP_001399108.1
TYW1B	NM_001412180.1	c.1447-2337G>T		intron_variant			NP_001399109.1
TYW1B	NM_001412182.1	c.664-2337G>T		intron_variant			NP_001399111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYW1B	ENST00000620995.5	c.1786-2337G>T		intron_variant		1	NM_001145440.3	ENSP00000482502	P1
TYW1B	ENST00000612372.4	c.1300-19168G>T		intron_variant		1		ENSP00000480534

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68219 AN: 151110 Hom.: 17401 Cov.: 30

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.452 AC: 68314 AN: 151228 Hom.: 17445 Cov.: 30 AF XY: 0.451 AC XY: 33296 AN XY: 73820

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.433

Alfa AF: 0.372 Hom.: 4581

Bravo AF: 0.473

Asia WGS AF: 0.510 AC: 1774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.63

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: rs4318932; hg19: chr7-72043041;