Variant X-110676341-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001143981.2(CHRDL1):c.1267G>A(p.Glu423Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000119 in 1,096,353 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000012 ( 0 hom. 4 hem. )

Consequence

CHRDL1
NM_001143981.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46

Variant links:

Genes affected

CHRDL1 (HGNC:29861): (chordin like 1) This gene encodes an antagonist of bone morphogenetic protein 4. The encoded protein may play a role in topographic retinotectal projection and in the regulation of retinal angiogenesis in response to hypoxia. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jan 2009]

CHRDL1 links:

CHRDL1 (HGNC:):

CHRDL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRDL1	NM_001143981.2 linkuse as main transcript	c.1267G>A	p.Glu423Lys	missense_variant	12/12	ENST00000372042.6	NP_001137453.1	Q9BU40-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRDL1	ENST00000372042.6 linkuse as main transcript	c.1267G>A	p.Glu423Lys	missense_variant	12/12	2	NM_001143981.2	ENSP00000361112.1		Q9BU40-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000549

AC:

AN:

182156

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66836

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000119

AC:

AN:

1096353

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

362013

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000155

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.1267G>A (p.E423K) alteration is located in exon 12 (coding exon 11) of the CHRDL1 gene. This alteration results from a G to A substitution at nucleotide position 1267, causing the glutamic acid (E) at amino acid position 423 to be replaced by a lysine (K). 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

Uncertain

0.44

BayesDel_addAF

Benign

0.00038

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.;.;.;.

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

D;D;D;D;D

M_CAP

Pathogenic

0.40

MetaRNN

Uncertain

0.44

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.97

L;.;.;.;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.080

N;N;N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.011

D;D;D;D;D

Sift4G

Benign

0.061

T;T;T;T;T

Polyphen

0.55

P;.;.;.;.

Vest4

0.54

MutPred

0.55

Gain of MoRF binding (P = 0.0022);.;.;.;.;

MVP

0.19

MPC

0.45

ClinPred

0.52

GERP RS

4.8

Varity_R

0.22

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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