3-129272155-T-C

Position:

chr3-129272155-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_016128.4(COPG1):c.1987-89T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,268,236 control chromosomes in the GnomAD database, including 20,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 7774 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12616 hom. )

Consequence

COPG1
NM_016128.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.26

Variant links:

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 links:

MIR6826 (HGNC:50001): (microRNA 6826) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6826 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-129272155-T-C is Benign according to our data. Variant chr3-129272155-T-C is described in ClinVar as [Benign]. Clinvar id is 2688277.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COPG1	NM_016128.4 linkuse as main transcript	c.1987-89T>C		intron_variant		ENST00000314797.10	NP_057212.1
MIR6826	NR_106884.1 linkuse as main transcript	n.10T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
COPG1	ENST00000314797.10 linkuse as main transcript	c.1987-89T>C	intron_variant		1	NM_016128.4	ENSP00000325002	P1
MIR6826	ENST00000617808.1 linkuse as main transcript	n.10T>C	mature_miRNA_variant	1/1
COPG1	ENST00000509889.5 linkuse as main transcript	c.32-193T>C	intron_variant		5		ENSP00000422478
COPG1	ENST00000515725.5 linkuse as main transcript	n.2246-89T>C	intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37566

AN:

152036

Hom.:

7744

Cov.:

show subpopulations

Gnomad AFR

AF:

0.565

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.0802

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.225

GnomAD3 exomes

AF:

0.162

AC:

32013

AN:

198148

Hom.:

4002

AF XY:

0.152

AC XY:

15974

AN XY:

104988

show subpopulations

Gnomad AFR exome

AF:

0.571

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.121

Gnomad SAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.0796

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.127

AC:

141408

AN:

1116082

Hom.:

12616

Cov.:

AF XY:

0.128

AC XY:

71705

AN XY:

561738

show subpopulations

Gnomad4 AFR exome

AF:

0.582

Gnomad4 AMR exome

AF:

0.172

Gnomad4 ASJ exome

AF:

0.185

Gnomad4 EAS exome

AF:

0.0918

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.0842

Gnomad4 NFE exome

AF:

0.106

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.247

AC:

37658

AN:

152154

Hom.:

7774

Cov.:

AF XY:

0.242

AC XY:

18000

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.565

Gnomad4 AMR

AF:

0.193

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.190

Gnomad4 FIN

AF:

0.0802

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.215

Hom.:

1435

Bravo

AF:

0.271

Asia WGS

AF:

0.191

AC:

661

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 27% of patients studied by a panel of primary immunodeficiencies. Number of patients: 26. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.56

DANN

Benign

0.47

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over