1-111315282-G-C

Variant names:

• chr1-111315282-G-C
• rs767626173
• ENST00000430615.1:c.3G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The ENST00000430615.1(CHIA):​c.3G>C​(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000411 in 1,459,876 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CHIA ENST00000430615.1 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.82
• Publications: 0 publications found

Genes affected

CHIA (HGNC:17432): (chitinase acidic) The protein encoded by this gene degrades chitin, which is found in the cell wall of most fungi as well as in arthropods and some nematodes. The encoded protein can also stimulate interleukin 13 expression, and variations in this gene can lead to asthma susceptibility. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 54 codons. Genomic position: 111317684. Lost 0.145 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIA	NM_201653.4	c.327G>C	p.Met109Ile	missense_variant	Exon 6 of 12	ENST00000369740.6	NP_970615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIA	ENST00000369740.6	c.327G>C	p.Met109Ile	missense_variant	Exon 6 of 12	1	NM_201653.4	ENSP00000358755.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459876 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726268

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4358

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111750

Other (OTH) AF: 0.00 AC: 0 AN: 60234

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T;T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;.;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.49	T;T;T;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	.;M;M;.
PhyloP100		4.8
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Benign	0.14
Sift	Benign	0.092	T;D;D;D
Sift4G	Uncertain	0.040	D;T;T;D
Polyphen		0.50	.;P;P;.
Vest4		0.65, 0.65, 0.82
MutPred		0.69		.;Gain of catalytic residue at M109 (P = 0.0126);Gain of catalytic residue at M109 (P = 0.0126);.;
MVP		0.29
MPC		0.12
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.92
gMVP		0.80
Mutation Taster		=97/103	disease causing

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: rs767626173; hg19: chr1-111857904;