rs722579

Variant names:

• chr16-70494321-C-T
• rs722579
• NM_015386.3:c.1647+1945G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015386.3(COG4):​c.1647+1945G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,948 control chromosomes in the GnomAD database, including 12,624 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12624 hom., cov: 32)
• Consequence: COG4 NM_015386.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774
• Publications: 9 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, PanelApp Australia
• microcephalic osteodysplastic dysplasia, Saul-Wilson type

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.64 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.1647+1945G>A		intron	N/A	NP_056201.2	J3KNI1
	COG4	NM_001195139.2		c.1635+1945G>A		intron	N/A	NP_001182068.2	A0A6I8PIQ6
	COG4	NM_001365426.1		c.1221+1945G>A		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.1647+1945G>A		intron	N/A	ENSP00000315775.5	J3KNI1
	COG4	ENST00000393612.8	TSL:1	c.1647+1945G>A		intron	N/A	ENSP00000377236.5	A0A0A0MS45
	COG4	ENST00000530314.5	TSL:1	n.2326+1945G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60654 AN: 151830 Hom.: 12615 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.426

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.399 AC: 60686 AN: 151948 Hom.: 12624 Cov.: 32 AF XY: 0.404 AC XY: 29982 AN XY: 74232

African (AFR) AF: 0.303 AC: 12545 AN: 41452

American (AMR) AF: 0.450 AC: 6864 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1480 AN: 3464

East Asian (EAS) AF: 0.577 AC: 2976 AN: 5162

South Asian (SAS) AF: 0.659 AC: 3180 AN: 4824

European-Finnish (FIN) AF: 0.351 AC: 3699 AN: 10536

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28565 AN: 67958

Other (OTH) AF: 0.427 AC: 897 AN: 2102

Alfa AF: 0.419 Hom.: 17441

Bravo AF: 0.400

Asia WGS AF: 0.625 AC: 2174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.47
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs722579; hg19: chr16-70528224;