11-14468728-T-A

Position:

• chr11-14468728-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144061.2(COPB1):​c.2098A>T​(p.Thr700Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COPB1 NM_001144061.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.00

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1384502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COPB1	NM_001144061.2	c.2098A>T	p.Thr700Ser	missense_variant	16/22	ENST00000439561.7	NP_001137533.1
COPB1	NM_001144062.2	c.2098A>T	p.Thr700Ser	missense_variant	16/22		NP_001137534.1
COPB1	NM_016451.5	c.2098A>T	p.Thr700Ser	missense_variant	16/22		NP_057535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COPB1	ENST00000439561.7	c.2098A>T	p.Thr700Ser	missense_variant	16/22	1	NM_001144061.2	ENSP00000397873	P1
COPB1	ENST00000249923.7	c.2098A>T	p.Thr700Ser	missense_variant	16/22	1		ENSP00000249923	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.2098A>T (p.T700S) alteration is located in exon 16 (coding exon 15) of the COPB1 gene. This alteration results from a A to T substitution at nucleotide position 2098, causing the threonine (T) at amino acid position 700 to be replaced by a serine (S). 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	Benign	0.077
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.87
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.032
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.33	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.070
Sift	Benign	0.78	T;T
Sift4G	Benign	0.77	T;T
Polyphen		0.0030	B;B
Vest4		0.42
MutPred		0.33		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.34
MPC		0.20
ClinPred		0.67	D
GERP RS		5.3
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.097
gMVP		0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs1850336925; hg19: chr11-14490274;