Variant X-110688673-G-A details in Genebe, Genetics Data Aggregator

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

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]

CHRDL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

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

Synonymous conserved (PhyloP=1.06 with no splicing effect.

BS1

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

High Hemizygotes in GnomAd4 at 31 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRDL1	NM_001143981.2 linkuse as main transcript	c.909C>T	p.Cys303=	synonymous_variant	9/12	ENST00000372042.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRDL1	ENST00000372042.6 linkuse as main transcript	c.909C>T	p.Cys303=	synonymous_variant	9/12	2	NM_001143981.2	A1	Q9BU40-4

Frequencies

GnomAD3 genomes

AF:

0.000857

AC:

AN:

109715

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

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.:

AF XY:

0.000913

AC XY:

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.:

Cov.:

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

AF:

0.000847

AC:

AN:

109762

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

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.:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 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.

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