dbSNP rs756784317: COBLL1:p.Gly940Cys (chr2-164694574-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365672.2(COBLL1):c.2818G>T(p.Gly940Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G940S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

COBLL1
NM_001365672.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.353

Publications

4 publications found

Variant links:

Genes affected

COBLL1 (HGNC:23571): (cordon-bleu WH2 repeat protein like 1) Enables cadherin binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

COBLL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.101872236).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365672.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COBLL1	NM_001365672.2	MANE Select	c.2818G>T	p.Gly940Cys	missense	Exon 12 of 14	NP_001352601.1	Q53SF7-4
COBLL1	NM_001278458.2		c.3133G>T	p.Gly1045Cys	missense	Exon 15 of 17	NP_001265387.1	A0A0D9SG04
COBLL1	NM_001278460.2		c.2956G>T	p.Gly986Cys	missense	Exon 12 of 14	NP_001265389.1	A0A0X1KG75

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COBLL1	ENST00000652658.2	MANE Select	c.2818G>T	p.Gly940Cys	missense	Exon 12 of 14	ENSP00000498242.1	Q53SF7-4
COBLL1	ENST00000409184.8	TSL:1	c.2956G>T	p.Gly986Cys	missense	Exon 12 of 14	ENSP00000387326.5	A0A0X1KG75
COBLL1	ENST00000342193.8	TSL:1	c.2932G>T	p.Gly978Cys	missense	Exon 12 of 14	ENSP00000341360.4	Q53SF7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

250886

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461642

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111884

Other (OTH)

AF:

0.0000331

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000412

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.7

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0036

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.54

M_CAP

Benign

0.0098

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.35

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.8

REVEL

Benign

0.12

Sift

Benign

0.056

Sift4G

Uncertain

0.027

Polyphen

0.96

Vest4

0.20

MutPred

0.25

Gain of sheet (P = 0.0827)

MVP

0.34

MPC

0.14

ClinPred

0.098

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.085

gMVP

0.14

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over