rs2253833

Variant names:

• chr7-107565224-C-T
• rs2253833
• NM_181581.3:c.-22+548C>T

Variant summary

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

The NM_181581.3(DUS4L):​c.-22+548C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,146 control chromosomes in the GnomAD database, including 3,367 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 0.20 (3367 hom., cov: 32)
• Consequence: DUS4L NM_181581.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• Publications: 9 publications found

Genes affected

DUS4L (HGNC:21517): (dihydrouridine synthase 4 like) Predicted to enable tRNA dihydrouridine synthase activity. Predicted to be involved in tRNA dihydrouridine synthesis. [provided by Alliance of Genome Resources, Apr 2022]

DUS4L-BCAP29 (HGNC:54422): (DUS4L-BCAP29 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring DUS4L (dihydrouridine synthase 4 like) and BCAP29 (B cell receptor associated protein 29) genes on chromosome 7. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2019]

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 (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUS4L	NM_181581.3	c.-22+548C>T		intron_variant	Intron 2 of 7	ENST00000265720.8	NP_853559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUS4L	ENST00000265720.8	c.-22+548C>T		intron_variant	Intron 2 of 7	2	NM_181581.3	ENSP00000265720.3
DUS4L-BCAP29	ENST00000673665.1	c.-22+548C>T		intron_variant	Intron 1 of 12			ENSP00000501082.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30416 AN: 152028 Hom.: 3360 Cov.: 32

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.200 AC: 30434 AN: 152146 Hom.: 3367 Cov.: 32 AF XY: 0.202 AC XY: 15003 AN XY: 74372

African (AFR) AF: 0.0950 AC: 3944 AN: 41512

American (AMR) AF: 0.240 AC: 3671 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 950 AN: 3470

East Asian (EAS) AF: 0.329 AC: 1705 AN: 5178

South Asian (SAS) AF: 0.134 AC: 649 AN: 4830

European-Finnish (FIN) AF: 0.249 AC: 2629 AN: 10574

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16185 AN: 67982

Other (OTH) AF: 0.198 AC: 418 AN: 2114

Alfa AF: 0.221 Hom.: 2337

Bravo AF: 0.200

Asia WGS AF: 0.232 AC: 807 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	1.5
DANN	Benign	0.43
PhyloP100		-0.41
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: rs2253833; hg19: chr7-107205669;