rs5943053

Variant names:

• chrX-110688628-T-C
• rs5943053
• NM_001143981.2:c.954A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-110688628-T-C
• chrX-110688628-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001143981.2(CHRDL1):​c.954A>G​(p.Lys318Lys) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.175
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• isolated congenital megalocornea

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 257558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143981.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRDL1	NM_001143981.2	MANE Select	c.954A>G	p.Lys318Lys	synonymous	Exon 9 of 12	NP_001137453.1
	CHRDL1	NM_001367204.1		c.954A>G	p.Lys318Lys	synonymous	Exon 9 of 12	NP_001354133.1
	CHRDL1	NM_001143982.2		c.951A>G	p.Lys317Lys	synonymous	Exon 9 of 12	NP_001137454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRDL1	ENST00000372042.6	TSL:2 MANE Select	c.954A>G	p.Lys318Lys	synonymous	Exon 9 of 12	ENSP00000361112.1
	CHRDL1	ENST00000444321.2	TSL:1	c.951A>G	p.Lys317Lys	synonymous	Exon 9 of 12	ENSP00000399739.2
	CHRDL1	ENST00000372045.5	TSL:1	c.933A>G	p.Lys311Lys	synonymous	Exon 9 of 12	ENSP00000361115.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 53247 AN: 109485 Hom.: 11253 Cov.: 22

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

GnomAD2 exomes AF: 0.343 AC: 62789 AN: 183161 AF XY: 0.334

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 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.: 31 AF XY: 0.372 AC XY: 135103 AN XY: 362769

African (AFR) AF: 0.807 AC: 21290 AN: 26384

American (AMR) AF: 0.188 AC: 6619 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 8759 AN: 19378

East Asian (EAS) AF: 0.00759 AC: 229 AN: 30182

South Asian (SAS) AF: 0.206 AC: 11136 AN: 54074

European-Finnish (FIN) AF: 0.389 AC: 15750 AN: 40508

Middle Eastern (MID) AF: 0.334 AC: 1380 AN: 4133

European-Non Finnish (NFE) AF: 0.398 AC: 334415 AN: 841167

Other (OTH) AF: 0.383 AC: 17640 AN: 46063

GnomAD4 genome AF: 0.486 AC: 53278 AN: 109532 Hom.: 11256 Cov.: 22 AF XY: 0.463 AC XY: 14760 AN XY: 31846

African (AFR) AF: 0.790 AC: 23742 AN: 30041

American (AMR) AF: 0.309 AC: 3147 AN: 10188

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1216 AN: 2618

East Asian (EAS) AF: 0.00913 AC: 32 AN: 3506

South Asian (SAS) AF: 0.215 AC: 541 AN: 2521

European-Finnish (FIN) AF: 0.391 AC: 2223 AN: 5680

Middle Eastern (MID) AF: 0.344 AC: 73 AN: 212

European-Non Finnish (NFE) AF: 0.404 AC: 21277 AN: 52617

Other (OTH) AF: 0.432 AC: 640 AN: 1481

Alfa AF: 0.441 Hom.: 5094

Bravo AF: 0.491

EpiCase AF: 0.402

EpiControl AF: 0.390

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.2
DANN	Benign	0.69
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5943053; hg19: chrX-109931856; COSMIC: COSV54324763;