Variant 22-41237312-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138481.2(CHADL):c.1760G>A(p.Gly587Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,228 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 0.0000066 ( 0 hom., cov: 33)

Consequence

CHADL
NM_138481.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.721

Variant links:

Genes affected

CHADL (HGNC:25165): (chondroadherin like) Enables collagen binding activity and collagen fibril binding activity. Involved in negative regulation of collagen fibril organization. Located in collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

CHADL links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055855036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHADL	NM_138481.2 linkuse as main transcript	c.1760G>A	p.Gly587Glu	missense_variant	3/6	ENST00000216241.14	NP_612490.1	Q6NUI6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHADL	ENST00000216241.14 linkuse as main transcript	c.1760G>A	p.Gly587Glu	missense_variant	3/6	1	NM_138481.2	ENSP00000216241.9	Q6NUI6-1
CHADL	ENST00000417999.5 linkuse as main transcript	c.1751G>A	p.Gly584Glu	missense_variant	2/5	5		ENSP00000392046.1	H0Y4I5
CHADL	ENST00000455425.1 linkuse as main transcript	c.251G>A	p.Gly84Glu	missense_variant	2/4	2		ENSP00000412359.1	B0QYT2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.1760G>A (p.G587E) alteration is located in exon 3 (coding exon 3) of the CHADL gene. This alteration results from a G to A substitution at nucleotide position 1760, causing the glycine (G) at amino acid position 587 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

2.0

DANN

Benign

0.47

DEOGEN2

Benign

0.0011

T;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.13

N;N

REVEL

Benign

0.073

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;.

Polyphen

0.0010

B;.

Vest4

0.035

MutPred

0.33

Loss of catalytic residue at T586 (P = 0.0881);.;

MVP

0.18

MPC

0.027

ClinPred

0.022

GERP RS

-4.7

Varity_R

0.049

gMVP

0.59

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over