chr1-203226561-G-A

Variant names:

• chr1-203226561-G-A
• rs2486070
• NM_003465.3:c.56-691C>T

Variant summary

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

The NM_003465.3(CHIT1):​c.56-691C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,134 control chromosomes in the GnomAD database, including 4,124 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 0.22 (4124 hom., cov: 31)
• Consequence: CHIT1 NM_003465.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIT1	NM_003465.3	c.56-691C>T		intron_variant	Intron 2 of 10	ENST00000367229.6	NP_003456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIT1	ENST00000367229.6	c.56-691C>T		intron_variant	Intron 2 of 10	1	NM_003465.3	ENSP00000356198.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32912 AN: 152016 Hom.: 4113 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.217 AC: 32955 AN: 152134 Hom.: 4124 Cov.: 31 AF XY: 0.222 AC XY: 16477 AN XY: 74386

African (AFR) AF: 0.226 AC: 9360 AN: 41500

American (AMR) AF: 0.271 AC: 4143 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 771 AN: 3472

East Asian (EAS) AF: 0.549 AC: 2834 AN: 5160

South Asian (SAS) AF: 0.433 AC: 2087 AN: 4822

European-Finnish (FIN) AF: 0.121 AC: 1282 AN: 10600

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11813 AN: 67984

Other (OTH) AF: 0.229 AC: 483 AN: 2112

Alfa AF: 0.195 Hom.: 1728

Bravo AF: 0.224

Asia WGS AF: 0.447 AC: 1552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.76
PhyloP100		0.0090
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: rs2486070; hg19: chr1-203195689;