X-110681668-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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 (★).

• 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.188

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: 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 GnomAd at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRDL1	NM_001143981.2	c.989-19A>G		intron_variant		ENST00000372042.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRDL1	ENST00000372042.6	c.989-19A>G		intron_variant		2	NM_001143981.2	A1

Frequencies

GnomAD3 genomes AF: 0.00236 AC: 266 AN: 112572 Hom.: 5 Cov.: 23 AF XY: 0.00265 AC XY: 92 AN XY: 34716

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.: 7 AF XY: 0.00259 AC XY: 143 AN XY: 55119

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.: 29 Cov.: 24 AF XY: 0.00141 AC XY: 456 AN XY: 323600

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.: 5 Cov.: 23 AF XY: 0.00262 AC XY: 91 AN XY: 34782

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.: 6

Bravo AF: 0.00281

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 17, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	12
Dann	Benign	0.89
La Branchor		0.41

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

Other links and lift over

dbSNP: rs149028104; hg19: chrX-109924896;