Genetic Variant COBLL1:p.Asn859His (chr2-164694817-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001365672.2(COBLL1):c.2575A>C(p.Asn859His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. N859D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

COBLL1
NM_001365672.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.24

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020588815).

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.2575A>C	p.Asn859His	missense	Exon 12 of 14	NP_001352601.1	Q53SF7-4
COBLL1	NM_001278458.2		c.2890A>C	p.Asn964His	missense	Exon 15 of 17	NP_001265387.1	A0A0D9SG04
COBLL1	NM_001278460.2		c.2713A>C	p.Asn905His	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.2575A>C	p.Asn859His	missense	Exon 12 of 14	ENSP00000498242.1	Q53SF7-4
COBLL1	ENST00000409184.8	TSL:1	c.2713A>C	p.Asn905His	missense	Exon 12 of 14	ENSP00000387326.5	A0A0X1KG75
COBLL1	ENST00000342193.8	TSL:1	c.2689A>C	p.Asn897His	missense	Exon 12 of 14	ENSP00000341360.4	Q53SF7-3

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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

GnomAD2 exomes

AF:

0.0000719

AC:

AN:

250438

AF XY:

0.0000517

show subpopulations

Gnomad AFR exome

AF:

0.00112

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1461684

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

33462

American (AMR)

AF:

0.0000224

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111948

Other (OTH)

AF:

0.0000166

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.000322

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00115

AC:

AN:

41562

American (AMR)

AF:

0.0000655

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.000234

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0067

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

M_CAP

Benign

0.024

MetaRNN

Benign

0.021

MetaSVM

Uncertain

-0.15

MutationAssessor

Uncertain

2.4

PhyloP100

3.2

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.2

REVEL

Benign

0.13

Sift

Benign

0.072

Sift4G

Uncertain

0.049

Polyphen

1.0

Vest4

0.11

MVP

0.59

MPC

0.077

ClinPred

0.086

GERP RS

6.0

Varity_R

0.11

gMVP

0.21

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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