rs9952504

Positions:

• chr18-657458-A-G

Variant summary

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

The NR_171001.1(TYMSOS):​n.450+384T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0772 in 261,410 control chromosomes in the GnomAD database, including 1,479 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 0.097 (1261 hom., cov: 31)
  • Exomes 𝑓: 0.050 (218 hom.)
• Consequence: TYMSOS NR_171001.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

Genes affected

TYMSOS (HGNC:29553): (TYMS opposite strand RNA)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYMSOS	NR_171001.1	n.450+384T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYMSOS	ENST00000585033.1	n.428+384T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14702 AN: 152032 Hom.: 1255 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.0828

Gnomad SAS AF: 0.0716

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0837

GnomAD4 exome AF: 0.0496 AC: 5418 AN: 109260 Hom.: 218 AF XY: 0.0479 AC XY: 2690 AN XY: 56122

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.0418

Gnomad4 ASJ exome AF: 0.0605

Gnomad4 EAS exome AF: 0.0762

Gnomad4 SAS exome AF: 0.0756

Gnomad4 FIN exome AF: 0.0253

Gnomad4 NFE exome AF: 0.0411

Gnomad4 OTH exome AF: 0.0617

GnomAD4 genome AF: 0.0970 AC: 14751 AN: 152150 Hom.: 1261 Cov.: 31 AF XY: 0.0953 AC XY: 7092 AN XY: 74388

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.0597

Gnomad4 EAS AF: 0.0828

Gnomad4 SAS AF: 0.0706

Gnomad4 FIN AF: 0.0392

Gnomad4 NFE AF: 0.0418

Gnomad4 OTH AF: 0.0857

Alfa AF: 0.0672 Hom.: 120

Bravo AF: 0.103

Asia WGS AF: 0.0820 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.0
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9952504; hg19: chr18-657458;