dbSNP rs767249917: CHRDL1:p.Lys314Arg (chrX-110688641-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001143981.2(CHRDL1):c.941A>G(p.Lys314Arg) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 20)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

CHRDL1
NM_001143981.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.66

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

isolated congenital megalocornea
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

CHRDL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143981.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHRDL1	NM_001143981.2	MANE Select	c.941A>G	p.Lys314Arg	missense	Exon 9 of 12	NP_001137453.1	Q9BU40-4
CHRDL1	NM_001367204.1		c.941A>G	p.Lys314Arg	missense	Exon 9 of 12	NP_001354133.1	Q9BU40-4
CHRDL1	NM_001143982.2		c.938A>G	p.Lys313Arg	missense	Exon 9 of 12	NP_001137454.1	Q9BU40-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHRDL1	ENST00000372042.6	TSL:2 MANE Select	c.941A>G	p.Lys314Arg	missense	Exon 9 of 12	ENSP00000361112.1	Q9BU40-4
CHRDL1	ENST00000444321.2	TSL:1	c.938A>G	p.Lys313Arg	missense	Exon 9 of 12	ENSP00000399739.2	Q9BU40-5
CHRDL1	ENST00000372045.5	TSL:1	c.920A>G	p.Lys307Arg	missense	Exon 9 of 12	ENSP00000361115.1	A0A452Q6Z9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000545

AC:

AN:

183377

AF XY:

0.0000147

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.11e-7

AC:

AN:

1097916

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26394

American (AMR)

AF:

0.00

AC:

AN:

35205

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19380

East Asian (EAS)

AF:

0.00

AC:

AN:

30199

South Asian (SAS)

AF:

0.00

AC:

AN:

54135

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841849

Other (OTH)

AF:

0.00

AC:

AN:

46084

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

0.0049

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.080

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.42

MutationAssessor

Benign

0.76

PhyloP100

7.7

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.39

Sift

Benign

0.040

Sift4G

Uncertain

0.053

Polyphen

1.0

Vest4

0.55

MutPred

0.38

Loss of methylation at K307 (P = 0.0137)

MVP

0.72

MPC

1.0

ClinPred

0.71

GERP RS

5.0

Varity_R

0.54

gMVP

0.60

Mutation Taster

=59/41

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over