Genetic Variant COBLL1:p.Ala891Thr (chr2-164694721-C-T) – 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.2671G>A(p.Ala891Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

COBLL1
NM_001365672.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00400

Publications

2 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:

Genome browser will be placed here

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=0.08334765).

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.2671G>A	p.Ala891Thr	missense	Exon 12 of 14	NP_001352601.1	Q53SF7-4
COBLL1	NM_001278458.2		c.2986G>A	p.Ala996Thr	missense	Exon 15 of 17	NP_001265387.1	A0A0D9SG04
COBLL1	NM_001278460.2		c.2809G>A	p.Ala937Thr	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.2671G>A	p.Ala891Thr	missense	Exon 12 of 14	ENSP00000498242.1	Q53SF7-4
COBLL1	ENST00000409184.8	TSL:1	c.2809G>A	p.Ala937Thr	missense	Exon 12 of 14	ENSP00000387326.5	A0A0X1KG75
COBLL1	ENST00000342193.8	TSL:1	c.2785G>A	p.Ala929Thr	missense	Exon 12 of 14	ENSP00000341360.4	Q53SF7-3

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

250290

AF XY:

0.0000148

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:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000602

AC:

AN:

1461668

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0000782

AC:

AN:

1111932

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41380

American (AMR)

AF:

0.00

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000895

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.6

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.014

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.74

M_CAP

Benign

0.0045

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

-0.0040

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.6

REVEL

Benign

0.030

Sift

Benign

0.12

Sift4G

Benign

0.24

Polyphen

0.42

Vest4

0.051

MVP

0.19

MPC

0.054

ClinPred

0.085

GERP RS

2.7

Varity_R

0.039

gMVP

0.23

Mutation Taster

=90/10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over