Variant rs2240089 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015198.5(COBL):c.2757C>G(p.His919Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,614,138 control chromosomes in the GnomAD database, including 25,045 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2198 hom., cov: 34)

Exomes 𝑓: 0.17 ( 22847 hom. )

Consequence

COBL
NM_015198.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.106

Variant links:

Genes affected

COBL (HGNC:22199): (cordon-bleu WH2 repeat protein) This gene encodes a protein that contains WH2 domains (WASP, Wiskott-Aldrich syndrome protein, homology domain-2) that interact with actin. The encoded actin regulator protein is required for growth and assembly of brush border microvilli that play a role in maintaining intestinal homeostasis. A similar protein in mouse functions in midbrain neural tube closure. A pseudogene of this gene is located on chromosome X. [provided by RefSeq, Oct 2016]

COBL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058608055).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COBL	NM_015198.5 linkuse as main transcript	c.2757C>G	p.His919Gln	missense_variant	10/13	ENST00000265136.12	NP_056013.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COBL	ENST00000265136.12 linkuse as main transcript	c.2757C>G	p.His919Gln	missense_variant	10/13	1	NM_015198.5	ENSP00000265136	P2	O75128-1

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24535

AN:

152146

Hom.:

2204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.394

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.199

GnomAD3 exomes

AF:

0.183

AC:

46106

AN:

251432

Hom.:

4715

AF XY:

0.188

AC XY:

25563

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.273

Gnomad EAS exome

AF:

0.299

Gnomad SAS exome

AF:

0.239

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.172

AC:

251137

AN:

1461874

Hom.:

22847

Cov.:

AF XY:

0.175

AC XY:

127104

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.265

Gnomad4 EAS exome

AF:

0.298

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.187

GnomAD4 genome

AF:

0.161

AC:

24525

AN:

152264

Hom.:

2198

Cov.:

AF XY:

0.162

AC XY:

12051

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.112

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.302

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.165

Gnomad4 OTH

AF:

0.199

Alfa

AF:

0.174

Hom.:

1872

Bravo

AF:

0.163

TwinsUK

AF:

0.171

AC:

635

ALSPAC

AF:

0.169

AC:

653

ESP6500AA

AF:

0.107

AC:

473

ESP6500EA

AF:

0.174

AC:

1496

ExAC

AF:

0.182

AC:

22108

Asia WGS

AF:

0.258

AC:

894

AN:

3478

EpiCase

AF:

0.169

EpiControl

AF:

0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.2

DANN

Benign

0.74

DEOGEN2

Benign

0.025

T;T;T;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.57

T;T;T;T

MetaRNN

Benign

0.0059

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

.;.;N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.6

N;N;N;.

REVEL

Benign

0.10

Sift

Benign

0.18

T;T;T;.

Sift4G

Benign

0.30

T;T;T;T

Polyphen

0.45, 0.40

.;.;P;B

Vest4

0.070, 0.055

MutPred

0.056

.;.;Loss of glycosylation at T915 (P = 0.1784);.;

MPC

0.085

ClinPred

0.0076

GERP RS

0.38

Varity_R

0.031

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over