rs1465306

Positions:

• chr7-67234797-T-C

Variant summary

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

The NM_018264.4(TYW1):​c.1978-3511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,900 control chromosomes in the GnomAD database, including 12,177 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 0.39 (12177 hom., cov: 31)
• Consequence: TYW1 NM_018264.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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]

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

LOC124901665 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYW1	NM_018264.4	c.1978-3511T>C		intron_variant		ENST00000359626.10	NP_060734.2
LOC124901665	XR_007060372.1	n.719+1437A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYW1	ENST00000359626.10	c.1978-3511T>C		intron_variant		1	NM_018264.4	ENSP00000352645	P1
PMS2P4	ENST00000685171.1	n.568+57666A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58568 AN: 151782 Hom.: 12147 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.386 AC: 58640 AN: 151900 Hom.: 12177 Cov.: 31 AF XY: 0.388 AC XY: 28831 AN XY: 74254

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.372

Alfa AF: 0.356 Hom.: 1901

Bravo AF: 0.401

Asia WGS AF: 0.384 AC: 1337 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.92
DANN	Benign	0.63

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: rs1465306; hg19: chr7-66699784;