chr11-14469353-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001144061.2(COPB1):​c.1948G>A​(p.Glu650Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

COPB1
NM_001144061.2 missense

Scores

3
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.62
Variant links:
Genes affected
COPB1 (HGNC:2231): (COPI coat complex subunit beta 1) This gene encodes a protein subunit of the coatomer complex associated with non-clathrin coated vesicles. The coatomer complex, also known as the coat protein complex 1, forms in the cytoplasm and is recruited to the Golgi by activated guanosine triphosphatases. Once at the Golgi membrane, the coatomer complex may assist in the movement of protein and lipid components back to the endoplasmic reticulum. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.38828176).
BS2
High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COPB1NM_001144061.2 linkc.1948G>A p.Glu650Lys missense_variant Exon 15 of 22 ENST00000439561.7 NP_001137533.1 P53618
COPB1NM_001144062.2 linkc.1948G>A p.Glu650Lys missense_variant Exon 15 of 22 NP_001137534.1 P53618
COPB1NM_016451.5 linkc.1948G>A p.Glu650Lys missense_variant Exon 15 of 22 NP_057535.1 P53618

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COPB1ENST00000439561.7 linkc.1948G>A p.Glu650Lys missense_variant Exon 15 of 22 1 NM_001144061.2 ENSP00000397873.2 P53618
COPB1ENST00000249923.7 linkc.1948G>A p.Glu650Lys missense_variant Exon 15 of 22 1 ENSP00000249923.3 P53618

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152176
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251168
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135760
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461540
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727112
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152176
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 13, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1948G>A (p.E650K) alteration is located in exon 15 (coding exon 14) of the COPB1 gene. This alteration results from a G to A substitution at nucleotide position 1948, causing the glutamic acid (E) at amino acid position 650 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.48
BayesDel_addAF
Uncertain
0.072
D
BayesDel_noAF
Benign
-0.13
CADD
Benign
22
DANN
Benign
0.96
DEOGEN2
Benign
0.20
T;T
Eigen
Benign
-0.046
Eigen_PC
Benign
0.20
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
.;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.39
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.95
L;L
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-1.7
N;N
REVEL
Benign
0.14
Sift
Benign
0.73
T;T
Sift4G
Benign
0.54
T;T
Polyphen
0.021
B;B
Vest4
0.66
MutPred
0.38
Loss of ubiquitination at K646 (P = 0.0142);Loss of ubiquitination at K646 (P = 0.0142);
MVP
0.73
MPC
0.25
ClinPred
0.97
D
GERP RS
5.7
Varity_R
0.34
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs778139308; hg19: chr11-14490899; API