rs1880278

Positions:

• chr7-67152573-T-C

Variant summary

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

The ENST00000359626.10(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 ENST00000359626.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

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:):

PMS2P4 (HGNC:9129): (PMS1 homolog 2, mismatch repair system component pseudogene 4)

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TYW1	NM_018264.4	c.1699-30553T>C		intron_variant		ENST00000359626.10	NP_060734.2
LOC124901666	XR_007060373.1	n.4931A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYW1	ENST00000359626.10	c.1699-30553T>C		intron_variant		1	NM_018264.4	ENSP00000352645	P1
PMS2P4	ENST00000685171.1	n.569-11871A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.0641

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.240

Alfa AF: 0.249 Hom.: 883

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

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: rs1880278; hg19: chr7-66617560;