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GeneBe

X-110688673-G-A

Variant summary

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

The NM_001143981.2(CHRDL1):c.909C>T(p.Cys303=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000711 in 1,206,068 control chromosomes in the GnomAD database, including 3 homozygotes. There are 259 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00085 ( 1 hom., 31 hem., cov: 20)
Exomes 𝑓: 0.00070 ( 2 hom. 228 hem. )

Consequence

CHRDL1
NM_001143981.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.06
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-110688673-G-A is Benign according to our data. Variant chrX-110688673-G-A is described in ClinVar as [Benign]. Clinvar id is 734280.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.06 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000847 (93/109762) while in subpopulation NFE AF= 0.000834 (44/52762). AF 95% confidence interval is 0.000638. There are 1 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAd at 32 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHRDL1NM_001143981.2 linkuse as main transcriptc.909C>T p.Cys303= synonymous_variant 9/12 ENST00000372042.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHRDL1ENST00000372042.6 linkuse as main transcriptc.909C>T p.Cys303= synonymous_variant 9/122 NM_001143981.2 A1Q9BU40-4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000857
AC:
94
AN:
109715
Hom.:
1
Cov.:
20
AF XY:
0.00100
AC XY:
32
AN XY:
31981
show subpopulations
Gnomad AFR
AF:
0.000233
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000493
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00631
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000853
Gnomad OTH
AF:
0.000684
GnomAD3 exomes
AF:
0.00102
AC:
187
AN:
183445
Hom.:
1
AF XY:
0.000913
AC XY:
62
AN XY:
67883
show subpopulations
Gnomad AFR exome
AF:
0.000228
Gnomad AMR exome
AF:
0.000365
Gnomad ASJ exome
AF:
0.00107
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00750
Gnomad NFE exome
AF:
0.000501
Gnomad OTH exome
AF:
0.00110
GnomAD4 exome
AF:
0.000697
AC:
764
AN:
1096306
Hom.:
2
Cov.:
30
AF XY:
0.000630
AC XY:
228
AN XY:
361696
show subpopulations
Gnomad4 AFR exome
AF:
0.0000759
Gnomad4 AMR exome
AF:
0.000312
Gnomad4 ASJ exome
AF:
0.00134
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00691
Gnomad4 NFE exome
AF:
0.000503
Gnomad4 OTH exome
AF:
0.000478
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000847
AC:
93
AN:
109762
Hom.:
1
Cov.:
20
AF XY:
0.000968
AC XY:
31
AN XY:
32038
show subpopulations
Gnomad4 AFR
AF:
0.000232
Gnomad4 AMR
AF:
0.000493
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00631
Gnomad4 NFE
AF:
0.000834
Gnomad4 OTH
AF:
0.000675
Alfa
AF:
0.000945
Hom.:
6
Bravo
AF:
0.000559
EpiCase
AF:
0.000600
EpiControl
AF:
0.000771

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 11, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
8.0
Dann
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs142726669; hg19: chrX-109931901; API