Variant X-110681668-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001143981.2(CHRDL1):c.989-19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,164,584 control chromosomes in the GnomAD database, including 34 homozygotes. There are 547 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0024 ( 5 hom., 91 hem., cov: 23)

Exomes 𝑓: 0.0015 ( 29 hom. 456 hem. )

Consequence

CHRDL1
NM_001143981.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.188

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant X-110681668-T-C is Benign according to our data. Variant chrX-110681668-T-C is described in ClinVar as [Benign]. Clinvar id is 1987026.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00235 (265/112628) while in subpopulation EAS AF= 0.017 (61/3582). AF 95% confidence interval is 0.0149. There are 5 homozygotes in gnomad4. There are 91 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRDL1	NM_001143981.2 linkuse as main transcript	c.989-19A>G		intron_variant		ENST00000372042.6	NP_001137453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRDL1	ENST00000372042.6 linkuse as main transcript	c.989-19A>G		intron_variant		2	NM_001143981.2	ENSP00000361112	A1	Q9BU40-4

Frequencies

GnomAD3 genomes

AF:

0.00236

AC:

266

AN:

112572

Hom.:

Cov.:

AF XY:

0.00265

AC XY:

AN XY:

34716

show subpopulations

Gnomad AFR

AF:

0.000517

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0169

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0170

Gnomad SAS

AF:

0.000365

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000937

Gnomad OTH

AF:

0.00197

GnomAD3 exomes

AF:

0.00392

AC:

656

AN:

167179

Hom.:

AF XY:

0.00259

AC XY:

143

AN XY:

55119

show subpopulations

Gnomad AFR exome

AF:

0.000312

Gnomad AMR exome

AF:

0.0183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0145

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.000195

Gnomad NFE exome

AF:

0.0000391

Gnomad OTH exome

AF:

0.00396

GnomAD4 exome

AF:

0.00152

AC:

1598

AN:

1051956

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

456

AN XY:

323600

show subpopulations

Gnomad4 AFR exome

AF:

0.000318

Gnomad4 AMR exome

AF:

0.0190

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0289

Gnomad4 SAS exome

AF:

0.000100

Gnomad4 FIN exome

AF:

0.000174

Gnomad4 NFE exome

AF:

0.0000483

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00235

AC:

265

AN:

112628

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

AN XY:

34782

show subpopulations

Gnomad4 AFR

AF:

0.000516

Gnomad4 AMR

AF:

0.0169

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0170

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000937

Gnomad4 OTH

AF:

0.00194

Alfa

AF:

0.000900

Hom.:

Bravo

AF:

0.00281

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 17, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.89

La Branchor

0.41

BranchPoint Hunter

1.0

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