chr1-111243390-T-A

Variant names:

• chr1-111243390-T-A
• rs1056831
• NM_004000.3:c.*176T>A

Variant summary

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

The NM_004000.3(CHI3L2):​c.*176T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 373,454 control chromosomes in the GnomAD database, including 15,657 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 0.25 (5594 hom., cov: 32)
  • Exomes 𝑓: 0.29 (10063 hom.)
• Consequence: CHI3L2 NM_004000.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.*176T>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.*176T>A		3_prime_UTR_variant	Exon 10 of 10		NP_001020368.1
CHI3L2	NM_001025199.2	c.*176T>A		3_prime_UTR_variant	Exon 10 of 10		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.*176T>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37962 AN: 151958 Hom.: 5599 Cov.: 32

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.292 AC: 64668 AN: 221378 Hom.: 10063 Cov.: 0 AF XY: 0.286 AC XY: 35490 AN XY: 124184

African (AFR) AF: 0.0921 AC: 511 AN: 5548

American (AMR) AF: 0.180 AC: 2349 AN: 13068

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1811 AN: 5564

East Asian (EAS) AF: 0.184 AC: 1574 AN: 8562

South Asian (SAS) AF: 0.224 AC: 10120 AN: 45156

European-Finnish (FIN) AF: 0.339 AC: 3160 AN: 9318

Middle Eastern (MID) AF: 0.278 AC: 231 AN: 832

European-Non Finnish (NFE) AF: 0.339 AC: 41632 AN: 122804

Other (OTH) AF: 0.312 AC: 3280 AN: 10526

GnomAD4 genome AF: 0.250 AC: 37954 AN: 152076 Hom.: 5594 Cov.: 32 AF XY: 0.246 AC XY: 18249 AN XY: 74304

African (AFR) AF: 0.0968 AC: 4019 AN: 41514

American (AMR) AF: 0.215 AC: 3285 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1205 AN: 3470

East Asian (EAS) AF: 0.198 AC: 1024 AN: 5162

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4814

European-Finnish (FIN) AF: 0.322 AC: 3403 AN: 10568

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23023 AN: 67962

Other (OTH) AF: 0.277 AC: 584 AN: 2112

Alfa AF: 0.298 Hom.: 931

Bravo AF: 0.234

Asia WGS AF: 0.238 AC: 828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.75
PhyloP100		0.25
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: rs1056831; hg19: chr1-111786012;