rs80122402

Variant names:

• chr7-107564287-G-C
• rs80122402
• ENST00000673665.1:c.-411G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000673665.1(DUS4L-BCAP29):​c.-411G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 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-BCAP29 ENST00000673665.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.420
• Publications: 0 publications found

Genes affected

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]

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]

COG5 Gene-Disease associations (from GenCC):

• COG5-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000673665.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUS4L	NM_181581.3	MANE Select	c.-111+78G>C		intron	N/A	NP_853559.1	O95620-1
	DUS4L-BCAP29	NM_001371364.2		c.-111+78G>C		intron	N/A	NP_001358293.1	A0A669KAY5
	DUS4L-BCAP29	NM_001371365.2		c.-111+40G>C		intron	N/A	NP_001358294.1	A0A669KB27

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUS4L-BCAP29	ENST00000673665.1		c.-411G>C		5_prime_UTR	Exon 1 of 13	ENSP00000501082.1	A0A669KB27
	DUS4L	ENST00000265720.8	TSL:2 MANE Select	c.-111+78G>C		intron	N/A	ENSP00000265720.3	O95620-1
	DUS4L	ENST00000467916.1	TSL:1	n.257G>C		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AF: 0.0295 AC: 259 AN: 8766

American (AMR) AF: 0.00234 AC: 33 AN: 14104

Ashkenazi Jewish (ASJ) AF: 0.000196 AC: 2 AN: 10192

East Asian (EAS) AF: 0.00 AC: 0 AN: 21054

South Asian (SAS) AF: 0.00 AC: 0 AN: 37950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20262

Middle Eastern (MID) AF: 0.000661 AC: 1 AN: 1514

European-Non Finnish (NFE) AF: 0.0000849 AC: 17 AN: 200146

Other (OTH) AF: 0.00169 AC: 33 AN: 19476

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

African (AFR) AF: 0.0323 AC: 1342 AN: 41570

American (AMR) AF: 0.00287 AC: 44 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00714 Hom.: 1

Bravo AF: 0.0103

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	COG5-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.8
DANN	Benign	0.61
PhyloP100		0.42
PromoterAI		-0.017	Neutral
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs80122402; hg19: chr7-107204732;