7-72804517-C-T

Variant names:

• chr7-72804517-C-T
• rs6945435
• NM_001145440.3:c.724-1995G>A

Variant summary

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

The NM_001145440.3(TYW1B):​c.724-1995G>A 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 151,874 control chromosomes in the GnomAD database, including 36,717 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 (36717 hom., cov: 31)
• Consequence: TYW1B NM_001145440.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (Cadd=1.495).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145440.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYW1B	NM_001145440.3	MANE Select	c.724-1995G>A		intron	N/A	NP_001138912.2	Q6NUM6-1
	TYW1B	NM_001412179.1		c.724-1995G>A		intron	N/A	NP_001399108.1
	TYW1B	NM_001412180.1		c.724-1995G>A		intron	N/A	NP_001399109.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYW1B	ENST00000620995.5	TSL:1 MANE Select	c.724-1995G>A		intron	N/A	ENSP00000482502.1	Q6NUM6-1
	TYW1B	ENST00000612372.4	TSL:1	c.238-1995G>A		intron	N/A	ENSP00000480534.1	A0A087WWV6
	TYW1B	ENST00000902318.1		c.724-1995G>A		intron	N/A	ENSP00000572377.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104259 AN: 151756 Hom.: 36712 Cov.: 31

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.687 AC: 104293 AN: 151874 Hom.: 36717 Cov.: 31 AF XY: 0.686 AC XY: 50900 AN XY: 74222

African (AFR) AF: 0.564 AC: 23331 AN: 41392

American (AMR) AF: 0.665 AC: 10137 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2511 AN: 3472

East Asian (EAS) AF: 0.446 AC: 2298 AN: 5158

South Asian (SAS) AF: 0.666 AC: 3200 AN: 4808

European-Finnish (FIN) AF: 0.791 AC: 8345 AN: 10552

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52088 AN: 67950

Other (OTH) AF: 0.688 AC: 1448 AN: 2106

Alfa AF: 0.725 Hom.: 4993

Bravo AF: 0.672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.5
PhyloP100		-0.97

Splicing

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

Other links and lift over

dbSNP: rs6945435;