7-107563544-T-G

Position:

• chr7-107563544-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006348.5(COG5):​c.94+259A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (56 hom., cov: 8)
  • Exomes 𝑓: 0.022 (51 hom.)
• Consequence: COG5 NM_006348.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.216

Genes affected

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-107563544-T-G is Benign according to our data. Variant chr7-107563544-T-G is described in ClinVar as [Benign]. Clinvar id is 1269259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG5	NM_006348.5	c.94+259A>C		intron_variant		ENST00000297135.9	NP_006339.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG5	ENST00000297135.9	c.94+259A>C		intron_variant		1	NM_006348.5	ENSP00000297135.4

Frequencies

GnomAD3 genomes AF: 0.0391 AC: 2301 AN: 58774 Hom.: 56 Cov.: 8

Gnomad AFR AF: 0.00814

Gnomad AMI AF: 0.0258

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0330

Gnomad EAS AF: 0.00124

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0822

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.0401

GnomAD4 exome AF: 0.0218 AC: 4275 AN: 196008 Hom.: 51 Cov.: 0 AF XY: 0.0212 AC XY: 2214 AN XY: 104552

Gnomad4 AFR exome AF: 0.00433

Gnomad4 AMR exome AF: 0.0146

Gnomad4 ASJ exome AF: 0.00769

Gnomad4 EAS exome AF: 0.0000887

Gnomad4 SAS exome AF: 0.0122

Gnomad4 FIN exome AF: 0.0272

Gnomad4 NFE exome AF: 0.0286

Gnomad4 OTH exome AF: 0.0220

GnomAD4 genome AF: 0.0391 AC: 2300 AN: 58836 Hom.: 56 Cov.: 8 AF XY: 0.0355 AC XY: 978 AN XY: 27550

Gnomad4 AFR AF: 0.00811

Gnomad4 AMR AF: 0.0328

Gnomad4 ASJ AF: 0.0330

Gnomad4 EAS AF: 0.00124

Gnomad4 SAS AF: 0.0558

Gnomad4 FIN AF: 0.0822

Gnomad4 NFE AF: 0.0797

Gnomad4 OTH AF: 0.0400

Alfa AF: 0.00198 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 13, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs71566734; hg19: chr7-107203989;