rs34049547

Variant names:

• chr1-111235708-G-A
• rs34049547
• NM_004000.3:c.550G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-111235708-G-A
• chr1-111235708-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004000.3(CHI3L2):​c.550G>A​(p.Val184Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,208 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00076 (7 hom.)
• Consequence: CHI3L2 NM_004000.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 7.82
• Publications: 4 publications found

Genes affected

CHI3L2 (HGNC:1933): (chitinase 3 like 2) The protein encoded by this gene is similar to bacterial chitinases but lacks chitinase activity. The encoded protein is secreted and is involved in cartilage biogenesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0061335266).
• BP6: Variant 1-111235708-G-A is Benign according to our data. Variant chr1-111235708-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 769524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0064 (975/152360) while in subpopulation AFR AF = 0.0221 (918/41584). AF 95% confidence interval is 0.0209. There are 7 homozygotes in GnomAd4. There are 463 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004000.3. 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
	CHI3L2	NM_004000.3	MANE Select	c.550G>A	p.Val184Ile	missense	Exon 6 of 11	NP_003991.2	Q15782-4
	CHI3L2	NM_001025197.1		c.520G>A	p.Val174Ile	missense	Exon 5 of 10	NP_001020368.1	Q15782-6
	CHI3L2	NM_001025199.2		c.313G>A	p.Val105Ile	missense	Exon 5 of 10	NP_001020370.1	Q15782-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L2	ENST00000369748.9	TSL:1 MANE Select	c.550G>A	p.Val184Ile	missense	Exon 6 of 11	ENSP00000358763.4	Q15782-4
	CHI3L2	ENST00000466741.5	TSL:1	c.313G>A	p.Val105Ile	missense	Exon 5 of 10	ENSP00000437086.1	Q15782-5
	CHI3L2	ENST00000445067.6	TSL:5	c.550G>A	p.Val184Ile	missense	Exon 8 of 13	ENSP00000437082.1	Q15782-4

Frequencies

GnomAD3 genomes AF: 0.00640 AC: 974 AN: 152242 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

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: 0.000118

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00192 AC: 482 AN: 251360 AF XY: 0.00136

Gnomad AFR exome AF: 0.0242

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000763 AC: 1115 AN: 1461848 Hom.: 7 Cov.: 35 AF XY: 0.000652 AC XY: 474 AN XY: 727222

African (AFR) AF: 0.0216 AC: 722 AN: 33474

American (AMR) AF: 0.00152 AC: 68 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86256

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.000186 AC: 207 AN: 1111982

Other (OTH) AF: 0.00132 AC: 80 AN: 60388

GnomAD4 genome AF: 0.00640 AC: 975 AN: 152360 Hom.: 7 Cov.: 33 AF XY: 0.00621 AC XY: 463 AN XY: 74514

African (AFR) AF: 0.0221 AC: 918 AN: 41584

American (AMR) AF: 0.00268 AC: 41 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68030

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00256 Hom.: 10

Bravo AF: 0.00773

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0238 AC: 105

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00243 AC: 295

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.8
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.023	D
Polyphen		0.99	D
Vest4		0.31
MVP		0.30
MPC		0.091
ClinPred		0.055	T
GERP RS		3.4
Varity_R		0.59
gMVP		0.22
Mutation Taster		=95/5	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: rs34049547; hg19: chr1-111778330;