Variant rs5943053 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001143981.2(CHRDL1):c.954A>G(p.Lys318=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,206,617 control chromosomes in the GnomAD database, including 70,319 homozygotes. There are 149,863 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 11256 hom., 14760 hem., cov: 22)

Exomes 𝑓: 0.38 ( 59063 hom. 135103 hem. )

Consequence

CHRDL1
NM_001143981.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.175

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant X-110688628-T-C is Benign according to our data. Variant chrX-110688628-T-C is described in ClinVar as [Benign]. Clinvar id is 257558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-110688628-T-C is described in Lovd as [Benign]. Variant chrX-110688628-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.175 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRDL1	NM_001143981.2 linkuse as main transcript	c.954A>G	p.Lys318=	synonymous_variant	9/12	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.954A>G	p.Lys318=	synonymous_variant	9/12	2	NM_001143981.2	ENSP00000361112	A1	Q9BU40-4

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

53247

AN:

109485

Hom.:

11253

Cov.:

AF XY:

0.463

AC XY:

14731

AN XY:

31789

show subpopulations

Gnomad AFR

AF:

0.790

Gnomad AMI

AF:

0.579

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.464

Gnomad EAS

AF:

0.00910

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.404

Gnomad OTH

AF:

0.438

GnomAD3 exomes

AF:

0.343

AC:

62789

AN:

183161

Hom.:

9185

AF XY:

0.334

AC XY:

22558

AN XY:

67633

show subpopulations

Gnomad AFR exome

AF:

0.798

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.456

Gnomad EAS exome

AF:

0.0100

Gnomad SAS exome

AF:

0.206

Gnomad FIN exome

AF:

0.379

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.358

GnomAD4 exome

AF:

0.380

AC:

417218

AN:

1097085

Hom.:

59063

Cov.:

AF XY:

0.372

AC XY:

135103

AN XY:

362769

show subpopulations

Gnomad4 AFR exome

AF:

0.807

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.452

Gnomad4 EAS exome

AF:

0.00759

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.389

Gnomad4 NFE exome

AF:

0.398

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.486

AC:

53278

AN:

109532

Hom.:

11256

Cov.:

AF XY:

0.463

AC XY:

14760

AN XY:

31846

show subpopulations

Gnomad4 AFR

AF:

0.790

Gnomad4 AMR

AF:

0.309

Gnomad4 ASJ

AF:

0.464

Gnomad4 EAS

AF:

0.00913

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.391

Gnomad4 NFE

AF:

0.404

Gnomad4 OTH

AF:

0.432

Alfa

AF:

0.441

Hom.:

5094

Bravo

AF:

0.491

EpiCase

AF:

0.402

EpiControl

AF:

0.390

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.2

DANN

Benign

0.69

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