chr3-129252908-C-T

Variant names:

• chr3-129252908-C-T
• rs73202214
• NM_016128.4:c.276C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_016128.4(COPG1):​c.276C>T​(p.Ile92Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,614,176 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (6 hom.)
• Consequence: COPG1 NM_016128.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.608
• Publications: 1 publications found

Genes affected

COPG1 (HGNC:2236): (COPI coat complex subunit gamma 1) Predicted to enable structural molecule activity. Predicted to be involved in several processes, including Golgi vesicle transport; establishment of Golgi localization; and organelle transport along microtubule. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

COPG1 Gene-Disease associations (from GenCC):

• non-severe combined immunodeficiency due to COPG1 deficiency

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 3-129252908-C-T is Benign according to our data. Variant chr3-129252908-C-T is described in ClinVar as Benign. ClinVar VariationId is 709572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.608 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016128.4. 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
	COPG1	NM_016128.4	MANE Select	c.276C>T	p.Ile92Ile	synonymous	Exon 5 of 24	NP_057212.1	Q9Y678

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPG1	ENST00000314797.10	TSL:1 MANE Select	c.276C>T	p.Ile92Ile	synonymous	Exon 5 of 24	ENSP00000325002.6	Q9Y678
	COPG1	ENST00000961557.1		c.276C>T	p.Ile92Ile	synonymous	Exon 5 of 25	ENSP00000631616.1
	COPG1	ENST00000865885.1		c.276C>T	p.Ile92Ile	synonymous	Exon 5 of 25	ENSP00000535944.1

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 238 AN: 152206 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00200

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00181 AC: 456 AN: 251470 AF XY: 0.00184

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.0145

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00203

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00169 AC: 2475 AN: 1461852 Hom.: 6 Cov.: 31 AF XY: 0.00175 AC XY: 1275 AN XY: 727226

African (AFR) AF: 0.000538 AC: 18 AN: 33480

American (AMR) AF: 0.00148 AC: 66 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 391 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86256

European-Finnish (FIN) AF: 0.000318 AC: 17 AN: 53416

Middle Eastern (MID) AF: 0.0102 AC: 59 AN: 5766

European-Non Finnish (NFE) AF: 0.00158 AC: 1752 AN: 1111982

Other (OTH) AF: 0.00262 AC: 158 AN: 60396

GnomAD4 genome AF: 0.00156 AC: 238 AN: 152324 Hom.: 3 Cov.: 32 AF XY: 0.00164 AC XY: 122 AN XY: 74486

African (AFR) AF: 0.000361 AC: 15 AN: 41568

American (AMR) AF: 0.00170 AC: 26 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00200 AC: 136 AN: 68034

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00257 Hom.: 1

Bravo AF: 0.00173

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs73202214; hg19: chr3-128971751; COSMIC: COSV100136116; COSMIC: COSV100136116;