chr7-72708751-G-A

Position:

• chr7-72708751-G-A

Variant summary

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

The NM_001145440.3(TYW1B):​c.1370+4870C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,062 control chromosomes in the GnomAD database, including 46,739 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 0.78 (46739 hom., cov: 31)
• Consequence: TYW1B NM_001145440.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYW1B	NM_001145440.3	c.1370+4870C>T		intron_variant		ENST00000620995.5
TYW1B	NM_001412179.1	c.1142+4870C>T		intron_variant
TYW1B	NM_001412180.1	c.1142+4870C>T		intron_variant
TYW1B	NM_001412182.1	c.248+4870C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYW1B	ENST00000620995.5	c.1370+4870C>T		intron_variant		1	NM_001145440.3	P1
TYW1B	ENST00000612372.4	c.884+4870C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118372 AN: 151944 Hom.: 46725 Cov.: 31

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.779 AC: 118418 AN: 152062 Hom.: 46739 Cov.: 31 AF XY: 0.776 AC XY: 57694 AN XY: 74356

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.777

Alfa AF: 0.814 Hom.: 6290

Bravo AF: 0.767

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3015844; hg19: chr7-72173704;