NM_001143981.2:c.610-2737G>C

Variant names:

• chrX-110697068-C-G
• rs5985545
• NM_001143981.2:c.610-2737G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143981.2(CHRDL1):​c.610-2737G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 110,175 control chromosomes in the GnomAD database, including 11,253 homozygotes. There are 15,070 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (11253 hom., 15070 hem., cov: 22)
• Consequence: CHRDL1 NM_001143981.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRDL1	NM_001143981.2	c.610-2737G>C		intron_variant	Intron 7 of 11	ENST00000372042.6	NP_001137453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRDL1	ENST00000372042.6	c.610-2737G>C		intron_variant	Intron 7 of 11	2	NM_001143981.2	ENSP00000361112.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 53430 AN: 110126 Hom.: 11250 Cov.: 22

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.00980

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.430

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.485 AC: 53464 AN: 110175 Hom.: 11253 Cov.: 22 AF XY: 0.462 AC XY: 15070 AN XY: 32595

African (AFR) AF: 0.792 AC: 23798 AN: 30043

American (AMR) AF: 0.310 AC: 3197 AN: 10326

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1202 AN: 2614

East Asian (EAS) AF: 0.00983 AC: 35 AN: 3559

South Asian (SAS) AF: 0.207 AC: 534 AN: 2580

European-Finnish (FIN) AF: 0.386 AC: 2253 AN: 5840

Middle Eastern (MID) AF: 0.329 AC: 70 AN: 213

European-Non Finnish (NFE) AF: 0.404 AC: 21350 AN: 52820

Other (OTH) AF: 0.425 AC: 643 AN: 1513

Alfa AF: 0.449 Hom.: 3217

Bravo AF: 0.492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.88
DANN	Benign	0.58
PhyloP100		-0.20
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: rs5985545; hg19: chrX-109940296;