1-111318646-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_201653.4(CHIA):c.883G>A(p.Ala295Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00134 in 1,614,114 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (16 hom.)
• Consequence: CHIA NM_201653.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.34

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032651424).
• BP6: Variant 1-111318646-G-A is Benign according to our data. Variant chr1-111318646-G-A is described in ClinVar as [Benign]. Clinvar id is 711969.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00636 (969/152334) while in subpopulation AFR AF= 0.0218 (907/41574). AF 95% confidence interval is 0.0206. There are 8 homozygotes in gnomad4. There are 485 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHIA	NM_201653.4	c.883G>A	p.Ala295Thr	missense_variant	9/12	ENST00000369740.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHIA	ENST00000369740.6	c.883G>A	p.Ala295Thr	missense_variant	9/12	1	NM_201653.4	P1
	ENST00000426321.1	n.149-719C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00635 AC: 967 AN: 152216 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00160 AC: 401 AN: 251078 Hom.: 4 AF XY: 0.00124 AC XY: 168 AN XY: 135666

Gnomad AFR exome AF: 0.0208

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000815 AC: 1191 AN: 1461780 Hom.: 16 Cov.: 32 AF XY: 0.000751 AC XY: 546 AN XY: 727190

Gnomad4 AFR exome AF: 0.0233

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000209

Gnomad4 OTH exome AF: 0.00162

GnomAD4 genome AF: 0.00636 AC: 969 AN: 152334 Hom.: 8 Cov.: 32 AF XY: 0.00651 AC XY: 485 AN XY: 74482

Gnomad4 AFR AF: 0.0218

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00128 Hom.: 3

Bravo AF: 0.00697

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0211 AC: 93

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00197 AC: 239

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	1.2
Dann	Benign	0.78
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.67	T;.;.;T;T;.;T;T
MetaRNN	Benign	0.0033	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	0.95	N;N;N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	4.3	N;N;N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	1.0	T;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T
Polyphen		0.0	.;.;B;.;B;.;.;.
Vest4		0.28, 0.29, 0.28, 0.29
MVP		0.27
MPC		0.026
ClinPred		0.014	T
GERP RS		4.8
Varity_R		0.11
gMVP		0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs79500525; hg19: chr1-111861268;