7-107564287-G-C

Position:

• chr7-107564287-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_181581.3(DUS4L):​c.-111+78G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 485,780 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (5 hom.)
• Consequence: DUS4L NM_181581.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.420

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:):

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-107564287-G-C is Benign according to our data. Variant chr7-107564287-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 908848.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00924 (1408/152316) while in subpopulation AFR AF= 0.0323 (1342/41570). AF 95% confidence interval is 0.0308. There are 22 homozygotes in gnomad4. There are 657 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUS4L	NM_181581.3	c.-111+78G>C		intron_variant		ENST00000265720.8
DUS4L-BCAP29	NR_163940.2	n.277+40G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUS4L	ENST00000265720.8	c.-111+78G>C		intron_variant		2	NM_181581.3	P1

Frequencies

GnomAD3 genomes AF: 0.00926 AC: 1409 AN: 152198 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.00103 AC: 345 AN: 333464 Hom.: 5 Cov.: 0 AF XY: 0.000886 AC XY: 155 AN XY: 174948

Gnomad4 AFR exome AF: 0.0295

Gnomad4 AMR exome AF: 0.00234

Gnomad4 ASJ exome AF: 0.000196

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000849

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.00924 AC: 1408 AN: 152316 Hom.: 22 Cov.: 32 AF XY: 0.00882 AC XY: 657 AN XY: 74480

Gnomad4 AFR AF: 0.0323

Gnomad4 AMR AF: 0.00287

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00714 Hom.: 1

Bravo AF: 0.0103

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

COG5-congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.8
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs80122402; hg19: chr7-107204732;