rs6460033

Positions:

• chr7-72798898-A-C
• chr7-72798898-A-G
• chr7-72798898-A-T

Variant summary

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

The NM_001145440.3(TYW1B):​c.846+3502T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,064 control chromosomes in the GnomAD database, including 36,789 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 0.69 (36789 hom., cov: 33)
• Consequence: TYW1B NM_001145440.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.964

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYW1B	NM_001145440.3	c.846+3502T>G		intron_variant		ENST00000620995.5	NP_001138912.2
TYW1B	NM_001412179.1	c.846+3502T>G		intron_variant			NP_001399108.1
TYW1B	NM_001412180.1	c.846+3502T>G		intron_variant			NP_001399109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYW1B	ENST00000620995.5	c.846+3502T>G		intron_variant		1	NM_001145440.3	ENSP00000482502.1
TYW1B	ENST00000612372.4	c.360+3502T>G		intron_variant		1		ENSP00000480534.1
TYW1B	ENST00000610600.1	c.651+3502T>G		intron_variant		2		ENSP00000484480.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104400 AN: 151946 Hom.: 36784 Cov.: 33

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.687 AC: 104434 AN: 152064 Hom.: 36789 Cov.: 33 AF XY: 0.686 AC XY: 50988 AN XY: 74354

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.689

Alfa AF: 0.740 Hom.: 12588

Bravo AF: 0.673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	7.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6460033; hg19: chr7-72263918;