rs2274147

Positions:

• chr1-52435151-A-G

Variant summary

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

The NM_001009881.3(TUT4):​c.4263+214T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 350,092 control chromosomes in the GnomAD database, including 19,152 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 0.35 (13039 hom., cov: 32)
  • Exomes 𝑓: 0.23 (6113 hom.)
• Consequence: TUT4 NM_001009881.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

Genes affected

TUT4 (HGNC:28981): (terminal uridylyl transferase 4) Enables RNA uridylyltransferase activity. Involved in RNA metabolic process; negative regulation of transposition, RNA-mediated; and stem cell population maintenance. Located in cytoplasmic ribonucleoprotein granule; cytosol; and nucleolus. Implicated in liver benign neoplasm. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUT4	NM_001009881.3	c.4263+214T>C		intron_variant		ENST00000257177.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUT4	ENST00000257177.9	c.4263+214T>C		intron_variant		1	NM_001009881.3	P4

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53383 AN: 152012 Hom.: 12999 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.228 AC: 45153 AN: 197962 Hom.: 6113 Cov.: 4 AF XY: 0.226 AC XY: 22887 AN XY: 101134

Gnomad4 AFR exome AF: 0.700

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.351 AC: 53471 AN: 152130 Hom.: 13039 Cov.: 32 AF XY: 0.346 AC XY: 25728 AN XY: 74370

Gnomad4 AFR AF: 0.703

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.281

Alfa AF: 0.294 Hom.: 1511

Bravo AF: 0.364

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.94
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2274147; hg19: chr1-52900823;