1-203237117-C-T

Variant names:

• chr1-203237117-C-T
• rs12747110
• ENST00000484834.5:n.4382+3346G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000484834.5(CHIT1):​n.4382+3346G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 152,342 control chromosomes in the GnomAD database, including 12 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 0.010 (12 hom., cov: 32)
• Consequence: CHIT1 ENST00000484834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0104 (1583/152342) while in subpopulation NFE AF= 0.0178 (1214/68026). AF 95% confidence interval is 0.017. There are 12 homozygotes in gnomad4. There are 699 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIT1	ENST00000484834.5	n.4382+3346G>A		intron_variant	Intron 3 of 11	2
CHIT1	ENST00000513472.5	n.151+3346G>A		intron_variant	Intron 3 of 7	3

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1584 AN: 152224 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.00489

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.00813

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

GnomAD4 genome AF: 0.0104 AC: 1583 AN: 152342 Hom.: 12 Cov.: 32 AF XY: 0.00938 AC XY: 699 AN XY: 74504

Gnomad4 AFR AF: 0.00325

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0130

Gnomad4 FIN AF: 0.00489

Gnomad4 NFE AF: 0.0178

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.0128 Hom.: 1

Bravo AF: 0.00989

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.33
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12747110; hg19: chr1-203206245;