rs1880278

Variant names:

• chr7-67152573-T-C
• rs1880278
• NM_018264.4:c.1699-30553T>C

Variant summary

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

The NM_018264.4(TYW1):​c.1699-30553T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,082 control chromosomes in the GnomAD database, including 5,596 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 0.26 (5596 hom., cov: 32)
• Consequence: TYW1 NM_018264.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519
• Publications: 7 publications found

Genes affected

TYW1 (HGNC:25598): (tRNA-yW synthesizing protein 1 homolog) Wybutosine (yW) is a hypermodified guanosine found in phenylalanine tRNA adjacent to the anticodon that stabilizes codon-anticodon interactions in the ribosome. In yeast, the homolog of this gene is essential for the synthesis of wybutosine. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

LOC124901666 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYW1	NM_018264.4	c.1699-30553T>C		intron_variant	Intron 13 of 15	ENST00000359626.10	NP_060734.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYW1	ENST00000359626.10	c.1699-30553T>C		intron_variant	Intron 13 of 15	1	NM_018264.4	ENSP00000352645.5

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39397 AN: 151964 Hom.: 5591 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0643

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.259 AC: 39423 AN: 152082 Hom.: 5596 Cov.: 32 AF XY: 0.254 AC XY: 18884 AN XY: 74368

African (AFR) AF: 0.376 AC: 15599 AN: 41452

American (AMR) AF: 0.210 AC: 3210 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3472

East Asian (EAS) AF: 0.0641 AC: 332 AN: 5180

South Asian (SAS) AF: 0.286 AC: 1378 AN: 4820

European-Finnish (FIN) AF: 0.143 AC: 1517 AN: 10608

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.230 AC: 15600 AN: 67968

Other (OTH) AF: 0.240 AC: 507 AN: 2112

Alfa AF: 0.253 Hom.: 936

Bravo AF: 0.265

Asia WGS AF: 0.201 AC: 703 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	2.0
DANN	Benign	0.27
PhyloP100		-0.52
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: rs1880278; hg19: chr7-66617560;