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

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

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 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 rank	MANE	Protein	UniProt
CHRDL1	NM_001143981.2	c.954A>G	p.Lys318Lys	synonymous_variant	Exon 9 of 12	ENST00000372042.6	NP_001137453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRDL1	ENST00000372042.6	c.954A>G	p.Lys318Lys	synonymous_variant	Exon 9 of 12	2	NM_001143981.2	ENSP00000361112.1

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

Gnomad4 AFR exome AF: 0.807 AC: 21290 AN: 26384

Gnomad4 AMR exome AF: 0.188 AC: 6619 AN: 35196

Gnomad4 ASJ exome AF: 0.452 AC: 8759 AN: 19378

Gnomad4 EAS exome AF: 0.00759 AC: 229 AN: 30182

Gnomad4 SAS exome AF: 0.206 AC: 11136 AN: 54074

Gnomad4 FIN exome AF: 0.389 AC: 15750 AN: 40508

Gnomad4 NFE exome AF: 0.398 AC: 334415 AN: 841167

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.790 AC: 0.79032 AN: 0.79032

Gnomad4 AMR AF: 0.309 AC: 0.308893 AN: 0.308893

Gnomad4 ASJ AF: 0.464 AC: 0.464477 AN: 0.464477

Gnomad4 EAS AF: 0.00913 AC: 0.00912721 AN: 0.00912721

Gnomad4 SAS AF: 0.215 AC: 0.214597 AN: 0.214597

Gnomad4 FIN AF: 0.391 AC: 0.391373 AN: 0.391373

Gnomad4 NFE AF: 0.404 AC: 0.404375 AN: 0.404375

Gnomad4 OTH AF: 0.432 AC: 0.43214 AN: 0.43214

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

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.2
DANN	Benign	0.69
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

Publications

LitVar

Other links and lift over

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