1-111319154-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.950G>A(p.Gly317Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,612,148 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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: 33)
  • Exomes 𝑓: 0.00082 (16 hom.)
• Consequence: CHIA NM_201653.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.05

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=0.006751001).
• BP6: Variant 1-111319154-G-A is Benign according to our data. Variant chr1-111319154-G-A is described in ClinVar as [Benign]. Clinvar id is 711970.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00645 (969/150298) while in subpopulation AFR AF= 0.0228 (907/39716). AF 95% confidence interval is 0.0216. There are 8 homozygotes in gnomad4. There are 487 alleles in male gnomad4 subpopulation. Median coverage is 33. 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.950G>A	p.Gly317Glu	missense_variant	10/12	ENST00000369740.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHIA	ENST00000369740.6	c.950G>A	p.Gly317Glu	missense_variant	10/12	1	NM_201653.4	P1
	ENST00000426321.1	n.149-1227C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00644 AC: 967 AN: 150198 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

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: 0.00824

GnomAD3 exomes AF: 0.00160 AC: 399 AN: 249240 Hom.: 4 AF XY: 0.00124 AC XY: 167 AN XY: 134972

Gnomad AFR exome AF: 0.0229

Gnomad AMR exome AF: 0.00114

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.000819 AC: 1197 AN: 1461850 Hom.: 16 Cov.: 62 AF XY: 0.000752 AC XY: 547 AN XY: 727238

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: 0.000214

Gnomad4 OTH exome AF: 0.00162

GnomAD4 genome AF: 0.00645 AC: 969 AN: 150298 Hom.: 8 Cov.: 33 AF XY: 0.00662 AC XY: 487 AN XY: 73532

Gnomad4 AFR AF: 0.0228

Gnomad4 AMR AF: 0.00230

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00815

Alfa AF: 0.00127 Hom.: 4

Bravo AF: 0.00697

ESP6500AA AF: 0.0211 AC: 93

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00198 AC: 240

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	0.067
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	0.0080
Dann	Benign	0.40
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.0068	T;.;.;T;T;.;T;T
MetaRNN	Benign	0.0068	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.5	N;N;N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	1.0	T;T;T;T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T;T;T;T
Polyphen		0.0	.;.;B;.;B;.;.;.
Vest4		0.070, 0.090, 0.091, 0.076
MVP		0.13
MPC		0.030
ClinPred		0.012	T
GERP RS		-9.8
Varity_R		0.25
gMVP		0.51

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: rs139812869; hg19: chr1-111861776;