16-23451984-C-G

Variant names:

• chr16-23451984-C-G
• rs394908
• NM_153603.4:c.169+842G>C

Variant summary

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

The NM_153603.4(COG7):​c.169+842G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,974 control chromosomes in the GnomAD database, including 2,431 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 0.18 (2431 hom., cov: 32)
• Consequence: COG7 NM_153603.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• Publications: 7 publications found

Genes affected

COG7 (HGNC:18622): (component of oligomeric golgi complex 7) The protein encoded by this gene resides in the golgi, and constitutes one of the 8 subunits of the conserved oligomeric Golgi (COG) complex, which is required for normal golgi morphology and localization. Mutations in this gene are associated with the congenital disorder of glycosylation type IIe.[provided by RefSeq, May 2010]

COG7 Gene-Disease associations (from GenCC):

• COG7-congenital disorder of glycosylation

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153603.4. 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
	COG7	NM_153603.4	MANE Select	c.169+842G>C		intron	N/A	NP_705831.1	A0A0S2Z652

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG7	ENST00000307149.10	TSL:1 MANE Select	c.169+842G>C		intron	N/A	ENSP00000305442.5	P83436
	COG7	ENST00000941095.1		c.169+842G>C		intron	N/A	ENSP00000611154.1
	COG7	ENST00000916651.1		c.169+842G>C		intron	N/A	ENSP00000586710.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26659 AN: 151856 Hom.: 2428 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.176 AC: 26685 AN: 151974 Hom.: 2431 Cov.: 32 AF XY: 0.179 AC XY: 13312 AN XY: 74278

African (AFR) AF: 0.174 AC: 7208 AN: 41446

American (AMR) AF: 0.153 AC: 2331 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3468

East Asian (EAS) AF: 0.290 AC: 1499 AN: 5172

South Asian (SAS) AF: 0.239 AC: 1150 AN: 4816

European-Finnish (FIN) AF: 0.223 AC: 2345 AN: 10524

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11154 AN: 67978

Other (OTH) AF: 0.167 AC: 352 AN: 2108

Alfa AF: 0.170 Hom.: 286

Bravo AF: 0.170

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		-0.64
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: rs394908; hg19: chr16-23463305;