chr7-67223811-A-G

Variant names:

• chr7-67223811-A-G
• rs4718487
• NM_018264.4:c.1978-14497A>G

Variant summary

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

The NM_018264.4(TYW1):​c.1978-14497A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 148,754 control chromosomes in the GnomAD database, including 28,561 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 0.62 (28561 hom., cov: 29)
• Consequence: TYW1 NM_018264.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 1 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]

ENSG00000291154 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYW1	NM_018264.4	c.1978-14497A>G		intron_variant	Intron 15 of 15	ENST00000359626.10	NP_060734.2
TYW1	NR_134540.2	n.2071-14497A>G		intron_variant	Intron 14 of 14
TYW1	XM_011516372.4	c.1978-2572A>G		intron_variant	Intron 15 of 15		XP_011514674.1
TYW1	XM_017012392.3	c.1696-14497A>G		intron_variant	Intron 12 of 12		XP_016867881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYW1	ENST00000359626.10	c.1978-14497A>G		intron_variant	Intron 15 of 15	1	NM_018264.4	ENSP00000352645.5

Frequencies

GnomAD3 genomes AF: 0.616 AC: 91617 AN: 148654 Hom.: 28545 Cov.: 29

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.616 AC: 91666 AN: 148754 Hom.: 28561 Cov.: 29 AF XY: 0.620 AC XY: 44999 AN XY: 72526

African (AFR) AF: 0.647 AC: 25956 AN: 40122

American (AMR) AF: 0.632 AC: 9445 AN: 14946

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2359 AN: 3422

East Asian (EAS) AF: 0.578 AC: 2960 AN: 5120

South Asian (SAS) AF: 0.587 AC: 2753 AN: 4692

European-Finnish (FIN) AF: 0.665 AC: 6822 AN: 10264

Middle Eastern (MID) AF: 0.715 AC: 206 AN: 288

European-Non Finnish (NFE) AF: 0.586 AC: 39250 AN: 66964

Other (OTH) AF: 0.623 AC: 1290 AN: 2072

Alfa AF: 0.599 Hom.: 3422

Bravo AF: 0.617

Asia WGS AF: 0.608 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.75
PhyloP100		-1.1
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: rs4718487; hg19: chr7-66688798;