21-18262820-A-C

Variant names:

• chr21-18262820-A-C
• rs765606559
• NM_024944.3:c.664A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024944.3(CHODL):​c.664A>C​(p.Ile222Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000436 in 1,604,948 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000046 (1 hom.)
• Consequence: CHODL NM_024944.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.49
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27323923).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024944.3. 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
	CHODL	NM_024944.3	MANE Select	c.664A>C	p.Ile222Leu	missense	Exon 5 of 6	NP_079220.2
	CHODL	NM_001204174.2		c.607A>C	p.Ile203Leu	missense	Exon 5 of 6	NP_001191103.1	Q9H9P2-4
	CHODL	NM_001204175.2		c.541A>C	p.Ile181Leu	missense	Exon 5 of 6	NP_001191104.1	Q9H9P2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHODL	ENST00000299295.7	TSL:1 MANE Select	c.664A>C	p.Ile222Leu	missense	Exon 5 of 6	ENSP00000299295.2	Q9H9P2-1
	CHODL	ENST00000400127.5	TSL:1	c.541A>C	p.Ile181Leu	missense	Exon 6 of 7	ENSP00000382992.1	Q9H9P2-2
	CHODL	ENST00000400131.5	TSL:1	c.511+2534A>C		intron	N/A	ENSP00000382996.1	A0A0C4DFS2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 250956 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000461 AC: 67 AN: 1452818 Hom.: 1 Cov.: 27 AF XY: 0.0000456 AC XY: 33 AN XY: 723454

African (AFR) AF: 0.00 AC: 0 AN: 33282

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39558

South Asian (SAS) AF: 0.00 AC: 0 AN: 85988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.0000598 AC: 66 AN: 1104310

Other (OTH) AF: 0.0000166 AC: 1 AN: 60084

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000227

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.5
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.092
Sift	Benign	0.12	T
Sift4G	Benign	0.13	T
Polyphen		0.60	P
Vest4		0.51
MutPred		0.34		Gain of catalytic residue at I222 (P = 0.0512)
MVP		0.14
MPC		0.096
ClinPred		0.51	D
GERP RS		5.4
Varity_R		0.29
gMVP		0.47
Mutation Taster		=80/20	polymorphism

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: rs765606559; hg19: chr21-19635137;