16-70482413-C-A

Variant names:

• chr16-70482413-C-A
• NM_015386.3:c.1921-238G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015386.3(COG4):​c.1921-238G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COG4 NM_015386.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 0 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), ClinGen, G2P, Orphanet, Ambry Genetics
• microcephalic osteodysplastic dysplasia, Saul-Wilson type

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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.1921-238G>T		intron	N/A	NP_056201.2	J3KNI1
	COG4	NM_001195139.2		c.1846-238G>T		intron	N/A	NP_001182068.2	A0A6I8PIQ6
	COG4	NM_001365426.1		c.1495-238G>T		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.1921-238G>T		intron	N/A	ENSP00000315775.5	J3KNI1
	COG4	ENST00000393612.8	TSL:1	c.1858-238G>T		intron	N/A	ENSP00000377236.5	A0A0A0MS45
	COG4	ENST00000530314.5	TSL:1	n.2600-238G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 467178 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 248840

African (AFR) AF: 0.00 AC: 0 AN: 13026

American (AMR) AF: 0.00 AC: 0 AN: 21912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14494

East Asian (EAS) AF: 0.00 AC: 0 AN: 31324

South Asian (SAS) AF: 0.00 AC: 0 AN: 47272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2254

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 280514

Other (OTH) AF: 0.00 AC: 0 AN: 26808

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.6
DANN	Benign	0.77
PhyloP100		-0.013
PromoterAI		-0.022	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-70516316;