7-107563995-C-T

Variant names:

• chr7-107563995-C-T
• rs55840928
• NM_181581.3:c.-325C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_181581.3(DUS4L):​c.-325C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,561,280 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (55 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (40 hom.)
• Consequence: DUS4L NM_181581.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.825

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]

COG5 (HGNC:14857): (component of oligomeric golgi complex 5) The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. The encoded protein is organized with conserved oligomeric Golgi complex components 6, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants. Mutations in this gene result in congenital disorder of glycosylation type 2I.[provided by RefSeq, Jan 2011]

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-107563995-C-T is Benign according to our data. Variant chr7-107563995-C-T is described in ClinVar as [Benign]. Clinvar id is 358480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2083/152268) while in subpopulation AFR AF= 0.0468 (1945/41562). AF 95% confidence interval is 0.0451. There are 55 homozygotes in gnomad4. There are 953 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUS4L	NM_181581.3	c.-325C>T		5_prime_UTR_variant	Exon 1 of 8	ENST00000265720.8	NP_853559.1
COG5	NM_006348.5	c.-99G>A		upstream_gene_variant		ENST00000297135.9	NP_006339.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUS4L	ENST00000265720	c.-325C>T		5_prime_UTR_variant	Exon 1 of 8	2	NM_181581.3	ENSP00000265720.3
DUS4L-BCAP29	ENST00000673757	c.-325C>T		5_prime_UTR_variant	Exon 1 of 15			ENSP00000501026.1
COG5	ENST00000297135.9	c.-99G>A		upstream_gene_variant		1	NM_006348.5	ENSP00000297135.4

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2077 AN: 152150 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00595

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00302 AC: 477 AN: 158134 Hom.: 7 AF XY: 0.00257 AC XY: 223 AN XY: 86614

Gnomad AFR exome AF: 0.0509

Gnomad AMR exome AF: 0.00248

Gnomad ASJ exome AF: 0.000834

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000852

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000161

Gnomad OTH exome AF: 0.00113

GnomAD4 exome AF: 0.00148 AC: 2083 AN: 1409012 Hom.: 40 Cov.: 38 AF XY: 0.00127 AC XY: 885 AN XY: 696618

Gnomad4 AFR exome AF: 0.0482

Gnomad4 AMR exome AF: 0.00305

Gnomad4 ASJ exome AF: 0.000594

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000184

Gnomad4 OTH exome AF: 0.00308

GnomAD4 genome AF: 0.0137 AC: 2083 AN: 152268 Hom.: 55 Cov.: 32 AF XY: 0.0128 AC XY: 953 AN XY: 74462

Gnomad4 AFR AF: 0.0468

Gnomad4 AMR AF: 0.00588

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00437 Hom.: 1

Bravo AF: 0.0161

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Dec 23, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

COG5-congenital disorder of glycosylation Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

COG5-related disorder Benign:1

Mar 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs55840928; hg19: chr7-107204440;