Variant 7-51025148-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_015198.5(COBL):c.3729C>T(p.Asp1243=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,611,598 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0028 ( 24 hom. )

Consequence

COBL
NM_015198.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.03

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 7-51025148-G-A is Benign according to our data. Variant chr7-51025148-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657504.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.03 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00283 (4133/1459662) while in subpopulation MID AF= 0.0239 (99/4144). AF 95% confidence interval is 0.0201. There are 24 homozygotes in gnomad4_exome. There are 2057 alleles in male gnomad4_exome subpopulation. Median coverage is 36. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COBL	NM_015198.5 linkuse as main transcript	c.3729C>T	p.Asp1243=	synonymous_variant	12/13	ENST00000265136.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COBL	ENST00000265136.12 linkuse as main transcript	c.3729C>T	p.Asp1243=	synonymous_variant	12/13	1	NM_015198.5	P2	O75128-1

Frequencies

GnomAD3 genomes

AF:

0.00479

AC:

727

AN:

151816

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00680

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00956

Gnomad ASJ

AF:

0.0283

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00234

Gnomad OTH

AF:

0.00959

GnomAD3 exomes

AF:

0.00427

AC:

1064

AN:

249078

Hom.:

AF XY:

0.00419

AC XY:

565

AN XY:

134756

show subpopulations

Gnomad AFR exome

AF:

0.00683

Gnomad AMR exome

AF:

0.00650

Gnomad ASJ exome

AF:

0.0285

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00307

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00260

Gnomad OTH exome

AF:

0.00900

GnomAD4 exome

AF:

0.00283

AC:

4133

AN:

1459662

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

2057

AN XY:

726148

show subpopulations

Gnomad4 AFR exome

AF:

0.00709

Gnomad4 AMR exome

AF:

0.00718

Gnomad4 ASJ exome

AF:

0.0288

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00299

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00186

Gnomad4 OTH exome

AF:

0.00654

GnomAD4 genome

AF:

0.00477

AC:

725

AN:

151936

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

360

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.00673

Gnomad4 AMR

AF:

0.00955

Gnomad4 ASJ

AF:

0.0283

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00234

Gnomad4 OTH

AF:

0.00949

Alfa

AF:

0.00549

Hom.:

Bravo

AF:

0.00559

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

COBL: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.2

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over