rs16970243

Variant names:

• chr16-70510030-G-C
• rs16970243
• NM_015386.3:c.739-9C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-70510030-G-C
• chr16-70510030-G-A
• chr16-70510030-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015386.3(COG4):​c.739-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 1,609,788 control chromosomes in the GnomAD database, including 6,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (3652 hom., cov: 32)
  • Exomes 𝑓: 0.013 (3189 hom.)
• Consequence: COG4 NM_015386.3 intron
• Scores: Splicing: ADA: 0.0002747
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.393
• Publications: 3 publications found

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]

COG4 Gene-Disease associations (from GenCC):

• COG4-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen
• microcephalic osteodysplastic dysplasia, Saul-Wilson type

  Inheritance: AD, AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 16-70510030-G-C is Benign according to our data. Variant chr16-70510030-G-C is described in ClinVar as Benign. ClinVar VariationId is 320377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015386.3. 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
	COG4	NM_015386.3	MANE Select	c.739-9C>G		intron	N/A	NP_056201.2	J3KNI1
	COG4	NM_001195139.2		c.727-9C>G		intron	N/A	NP_001182068.2	A0A6I8PIQ6
	COG4	NM_001365426.1		c.313-9C>G		intron	N/A	NP_001352355.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG4	ENST00000323786.10	TSL:1 MANE Select	c.739-9C>G		intron	N/A	ENSP00000315775.5	J3KNI1
	COG4	ENST00000393612.8	TSL:1	c.739-9C>G		intron	N/A	ENSP00000377236.5	A0A0A0MS45
	COG4	ENST00000530314.5	TSL:1	n.652-9C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18253 AN: 152042 Hom.: 3648 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00266

Gnomad OTH AF: 0.0798

GnomAD2 exomes AF: 0.0326 AC: 8169 AN: 250946 AF XY: 0.0242

Gnomad AFR exome AF: 0.417

Gnomad AMR exome AF: 0.0210

Gnomad ASJ exome AF: 0.0308

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00215

Gnomad OTH exome AF: 0.0189

GnomAD4 exome AF: 0.0133 AC: 19356 AN: 1457628 Hom.: 3189 Cov.: 29 AF XY: 0.0117 AC XY: 8458 AN XY: 725438

African (AFR) AF: 0.420 AC: 14065 AN: 33450

American (AMR) AF: 0.0230 AC: 1028 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 821 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.000778 AC: 67 AN: 86164

European-Finnish (FIN) AF: 0.0000938 AC: 5 AN: 53326

Middle Eastern (MID) AF: 0.0236 AC: 136 AN: 5754

European-Non Finnish (NFE) AF: 0.00134 AC: 1489 AN: 1108234

Other (OTH) AF: 0.0290 AC: 1745 AN: 60214

GnomAD4 genome AF: 0.120 AC: 18287 AN: 152160 Hom.: 3652 Cov.: 32 AF XY: 0.117 AC XY: 8695 AN XY: 74402

African (AFR) AF: 0.413 AC: 17141 AN: 41478

American (AMR) AF: 0.0449 AC: 685 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.00266 AC: 181 AN: 68016

Other (OTH) AF: 0.0789 AC: 167 AN: 2116

Alfa AF: 0.0116 Hom.: 48

Bravo AF: 0.135

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	COG4-congenital disorder of glycosylation (1)
-	-	1	COG4-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.6
DANN	Benign	0.78
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00027
dbscSNV1_RF	Benign	0.062
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

Other links and lift over

dbSNP: rs16970243; hg19: chr16-70543933;