chr1-203224006-T-G

Variant names:

• chr1-203224006-T-G
• rs2486068
• NM_003465.3:c.315-346A>C

Variant summary

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

The NM_003465.3(CHIT1):​c.315-346A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,016 control chromosomes in the GnomAD database, including 3,164 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 0.18 (3164 hom., cov: 32)
• Consequence: CHIT1 NM_003465.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 6 publications found

Genes affected

CHIT1 (HGNC:1936): (chitinase 1) Chitotriosidase is secreted by activated human macrophages and is markedly elevated in plasma of Gaucher disease patients. The expression of chitotriosidase occurs only at a late stage of differentiation of monocytes to activated macrophages in culture. Human macrophages can synthesize a functional chitotriosidase, a highly conserved enzyme with a strongly regulated expression. This enzyme may play a role in the degradation of chitin-containing pathogens. Several alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIT1	NM_003465.3	c.315-346A>C		intron_variant	Intron 4 of 10	ENST00000367229.6	NP_003456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIT1	ENST00000367229.6	c.315-346A>C		intron_variant	Intron 4 of 10	1	NM_003465.3	ENSP00000356198.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27243 AN: 151898 Hom.: 3156 Cov.: 32

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.179 AC: 27260 AN: 152016 Hom.: 3164 Cov.: 32 AF XY: 0.186 AC XY: 13792 AN XY: 74292

African (AFR) AF: 0.0964 AC: 3999 AN: 41496

American (AMR) AF: 0.258 AC: 3932 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 772 AN: 3470

East Asian (EAS) AF: 0.547 AC: 2817 AN: 5150

South Asian (SAS) AF: 0.427 AC: 2049 AN: 4800

European-Finnish (FIN) AF: 0.121 AC: 1276 AN: 10576

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.174 AC: 11813 AN: 67950

Other (OTH) AF: 0.203 AC: 427 AN: 2106

Alfa AF: 0.160 Hom.: 268

Bravo AF: 0.182

Asia WGS AF: 0.436 AC: 1515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.60
PhyloP100		-0.24
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: rs2486068; hg19: chr1-203193134;