16-70480925-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015386.3(COG4):c.*85T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,541,022 control chromosomes in the GnomAD database, including 219,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (19884 hom., cov: 31)
  • Exomes 𝑓: 0.53 (199474 hom.)
• Consequence: COG4 NM_015386.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.11

Genes affected

COG4 (HGNC:18620): (component of oligomeric golgi complex 4) The protein encoded by this gene is a component of an oligomeric protein complex involved in the structure and function of the Golgi apparatus. Defects in this gene may be a cause of congenital disorder of glycosylation type IIj. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-70480925-A-C is Benign according to our data. Variant chr16-70480925-A-C is described in ClinVar as [Benign]. Clinvar id is 1229189.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG4	NM_015386.3	c.*85T>G		3_prime_UTR_variant	19/19	ENST00000323786.10
COG4	NM_001195139.2	c.*85T>G		3_prime_UTR_variant	18/18
COG4	NM_001365426.1	c.*85T>G		3_prime_UTR_variant	20/20
COG4	NR_158212.1	n.2414T>G		non_coding_transcript_exon_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG4	ENST00000323786.10	c.*85T>G		3_prime_UTR_variant	19/19	1	NM_015386.3	P1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76981 AN: 151860 Hom.: 19873 Cov.: 31

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.532 AC: 739176 AN: 1389044 Hom.: 199474 Cov.: 22 AF XY: 0.527 AC XY: 365107 AN XY: 693276

Gnomad4 AFR exome AF: 0.422

Gnomad4 AMR exome AF: 0.459

Gnomad4 ASJ exome AF: 0.568

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.352

Gnomad4 FIN exome AF: 0.630

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.521

GnomAD4 genome AF: 0.507 AC: 77024 AN: 151978 Hom.: 19884 Cov.: 31 AF XY: 0.506 AC XY: 37599 AN XY: 74282

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.526

Alfa AF: 0.541 Hom.: 22400

Bravo AF: 0.497

Asia WGS AF: 0.370 AC: 1285 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.6
Dann	Benign	0.55
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: rs7919; hg19: chr16-70514828; COSMIC: COSV55369864; COSMIC: COSV55369864;