X-110695977-T-G

Variant names:

• chrX-110695977-T-G
• rs5943057
• NM_001143981.2:c.610-1646A>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.610-1646A>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 111,075 control chromosomes in the GnomAD database, including 11,290 homozygotes. There are 15,387 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 0.48 (11290 hom., 15387 hem., cov: 23)
• Consequence: CHRDL1 NM_001143981.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 7 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRDL1	NM_001143981.2	MANE Select	c.610-1646A>C		intron	N/A	NP_001137453.1	Q9BU40-4
	CHRDL1	NM_001367204.1		c.610-1646A>C		intron	N/A	NP_001354133.1	Q9BU40-4
	CHRDL1	NM_001143982.2		c.607-1646A>C		intron	N/A	NP_001137454.1	Q9BU40-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRDL1	ENST00000372042.6	TSL:2 MANE Select	c.610-1646A>C		intron	N/A	ENSP00000361112.1	Q9BU40-4
	CHRDL1	ENST00000444321.2	TSL:1	c.607-1646A>C		intron	N/A	ENSP00000399739.2	Q9BU40-5
	CHRDL1	ENST00000372045.5	TSL:1	c.589-1646A>C		intron	N/A	ENSP00000361115.1	A0A452Q6Z9

Frequencies

GnomAD3 genomes AF: 0.485 AC: 53819 AN: 111027 Hom.: 11287 Cov.: 23

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.00952

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.485 AC: 53851 AN: 111075 Hom.: 11290 Cov.: 23 AF XY: 0.460 AC XY: 15387 AN XY: 33419

African (AFR) AF: 0.790 AC: 23953 AN: 30314

American (AMR) AF: 0.308 AC: 3248 AN: 10536

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1227 AN: 2644

East Asian (EAS) AF: 0.00955 AC: 34 AN: 3562

South Asian (SAS) AF: 0.213 AC: 567 AN: 2656

European-Finnish (FIN) AF: 0.390 AC: 2334 AN: 5991

Middle Eastern (MID) AF: 0.338 AC: 72 AN: 213

European-Non Finnish (NFE) AF: 0.404 AC: 21390 AN: 52956

Other (OTH) AF: 0.420 AC: 640 AN: 1524

Alfa AF: 0.414 Hom.: 56893

Bravo AF: 0.492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.78
PhyloP100		-0.14
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: rs5943057; hg19: chrX-109939205;