rs2824577

Positions:

• chr21-17959812-A-G
• chr21-17959812-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204177.2(CHODL):​c.-45+42412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,028 control chromosomes in the GnomAD database, including 9,085 homozygotes. 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 0.34 (9085 hom., cov: 32)
• Consequence: CHODL NM_001204177.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466

Genes affected

CHODL (HGNC:17807): (chondrolectin) This gene encodes a type I membrane protein with a carbohydrate recognition domain characteristic of C-type lectins in its extracellular portion. In other proteins, this domain is involved in endocytosis of glycoproteins and exogenous sugar-bearing pathogens. This protein localizes predominantly to the perinuclear region. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHODL	NM_001204177.2	c.-45+42412A>G		intron_variant			NP_001191106.1
CHODL	NM_001204178.2	c.-145+42412A>G		intron_variant			NP_001191107.1
CHODL	NM_001204175.2	c.-45+42412A>G		intron_variant			NP_001191104.1
CHODL	NM_001204176.2	c.-145+42412A>G		intron_variant			NP_001191105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHODL	ENST00000400131.5	c.-45+42412A>G		intron_variant		1		ENSP00000382996.1
CHODL	ENST00000400135.5	c.-145+42412A>G		intron_variant		1		ENSP00000383001.1
CHODL	ENST00000400127.5	c.-145+42412A>G		intron_variant		1		ENSP00000382992.1
CHODL	ENST00000400128.5	c.-45+42412A>G		intron_variant		2		ENSP00000382993.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51496 AN: 151910 Hom.: 9070 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.339 AC: 51564 AN: 152028 Hom.: 9085 Cov.: 32 AF XY: 0.343 AC XY: 25533 AN XY: 74332

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.343

Alfa AF: 0.313 Hom.: 4189

Bravo AF: 0.342

Asia WGS AF: 0.487 AC: 1688 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2824577; hg19: chr21-19332129;