X-110694143-A-T

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.778+20T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000462 in 1,182,234 control chromosomes in the GnomAD database, including 1 homozygotes. There are 130 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 (0 hom., 62 hem., cov: 23)
  • Exomes 𝑓: 0.00026 (1 hom. 68 hem.)
• Consequence: CHRDL1 NM_001143981.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.754

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=-0.87).
• BP6: Variant X-110694143-A-T is Benign according to our data. Variant chrX-110694143-A-T is described in ClinVar as [Benign]. Clinvar id is 3022246.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00241 (269/111437) while in subpopulation AFR AF= 0.00858 (263/30647). AF 95% confidence interval is 0.00773. There are 0 homozygotes in gnomad4. There are 62 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 62 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRDL1	NM_001143981.2	c.778+20T>A		intron_variant		ENST00000372042.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRDL1	ENST00000372042.6	c.778+20T>A		intron_variant		2	NM_001143981.2	A1

Frequencies

GnomAD3 genomes AF: 0.00242 AC: 269 AN: 111385 Hom.: 0 Cov.: 23 AF XY: 0.00185 AC XY: 62 AN XY: 33575

Gnomad AFR AF: 0.00860

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000476

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000662

GnomAD3 exomes AF: 0.000702 AC: 123 AN: 175208 Hom.: 1 AF XY: 0.000465 AC XY: 28 AN XY: 60172

Gnomad AFR exome AF: 0.00838

Gnomad AMR exome AF: 0.000453

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000127

Gnomad OTH exome AF: 0.000232

GnomAD4 exome AF: 0.000259 AC: 277 AN: 1070797 Hom.: 1 Cov.: 24 AF XY: 0.000200 AC XY: 68 AN XY: 339723

Gnomad4 AFR exome AF: 0.00930

Gnomad4 AMR exome AF: 0.000373

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000366

Gnomad4 OTH exome AF: 0.000421

GnomAD4 genome AF: 0.00241 AC: 269 AN: 111437 Hom.: 0 Cov.: 23 AF XY: 0.00184 AC XY: 62 AN XY: 33637

Gnomad4 AFR AF: 0.00858

Gnomad4 AMR AF: 0.000476

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000654

Alfa AF: 0.00169 Hom.: 9

Bravo AF: 0.00292

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

May 02, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.22
Dann	Benign	0.47

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: rs139479571; hg19: chrX-109937371;