16-23445969-TAAAAAA-TAAAAAAA

Variant names:

• chr16-23445969-T-TA
• rs71379679
• NM_153603.4:c.170-9dupT

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP6 BS1

The NM_153603.4(COG7):​c.170-9dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,460,106 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 25)
  • Exomes 𝑓: 0.039 (0 hom.)
• Consequence: COG7 NM_153603.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.490
• Publications: 2 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Variant has high frequency in the NFE (0.0422) population. However there is too low homozygotes in high coverage region: (expected more than 472, got 0).
• BP6: Variant 16-23445969-T-TA is Benign according to our data. Variant chr16-23445969-T-TA is described in ClinVar as Benign. ClinVar VariationId is 3041322.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00197 (255/129254) while in subpopulation NFE AF = 0.00287 (172/59852). AF 95% confidence interval is 0.00252. There are 0 homozygotes in GnomAd4. There are 137 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.

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.170-9dupT		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.170-9_170-8insT		intron	N/A	ENSP00000305442.5	P83436
	COG7	ENST00000941095.1		c.170-9_170-8insT		intron	N/A	ENSP00000611154.1
	COG7	ENST00000916651.1		c.170-9_170-8insT		intron	N/A	ENSP00000586710.1

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 255 AN: 129224 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000800

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00166

Gnomad ASJ AF: 0.000644

Gnomad EAS AF: 0.000436

Gnomad SAS AF: 0.00218

Gnomad FIN AF: 0.00253

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00287

Gnomad OTH AF: 0.00173

GnomAD2 exomes AF: 0.0247 AC: 3770 AN: 152462 AF XY: 0.0246

Gnomad AFR exome AF: 0.0213

Gnomad AMR exome AF: 0.0282

Gnomad ASJ exome AF: 0.0332

Gnomad EAS exome AF: 0.0183

Gnomad FIN exome AF: 0.0185

Gnomad NFE exome AF: 0.0249

Gnomad OTH exome AF: 0.0292

GnomAD4 exome AF: 0.0393 AC: 52288 AN: 1330852 Hom.: 0 Cov.: 0 AF XY: 0.0377 AC XY: 25017 AN XY: 663272

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0341 AC: 999 AN: 29300

American (AMR) AF: 0.0280 AC: 1060 AN: 37898

Ashkenazi Jewish (ASJ) AF: 0.0370 AC: 894 AN: 24136

East Asian (EAS) AF: 0.0200 AC: 745 AN: 37224

South Asian (SAS) AF: 0.0249 AC: 1922 AN: 77314

European-Finnish (FIN) AF: 0.0242 AC: 993 AN: 40972

Middle Eastern (MID) AF: 0.0288 AC: 144 AN: 5002

European-Non Finnish (NFE) AF: 0.0425 AC: 43502 AN: 1023578

Other (OTH) AF: 0.0366 AC: 2029 AN: 55428

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00197 AC: 255 AN: 129254 Hom.: 0 Cov.: 25 AF XY: 0.00220 AC XY: 137 AN XY: 62204

African (AFR) AF: 0.000799 AC: 28 AN: 35050

American (AMR) AF: 0.00166 AC: 21 AN: 12628

Ashkenazi Jewish (ASJ) AF: 0.000644 AC: 2 AN: 3108

East Asian (EAS) AF: 0.000436 AC: 2 AN: 4586

South Asian (SAS) AF: 0.00219 AC: 9 AN: 4102

European-Finnish (FIN) AF: 0.00253 AC: 18 AN: 7120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.00287 AC: 172 AN: 59852

Other (OTH) AF: 0.00171 AC: 3 AN: 1750

Alfa AF: 0.0197 Hom.: 4

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	COG7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism

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: rs71379679; hg19: chr16-23457290; COSMIC: COSV56152672; COSMIC: COSV56152672;