Variant 11-883151-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023947.4(CHID1):c.956C>T(p.Ala319Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,457,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CHID1
NM_023947.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.202

Variant links:

Genes affected

CHID1 (HGNC:28474): (chitinase domain containing 1) Enables oligosaccharide binding activity. Involved in negative regulation of cytokine production involved in inflammatory response. Located in several cellular components, including late endosome; lysosome; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

CHID1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.103951335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHID1	NM_023947.4 linkuse as main transcript	c.956C>T	p.Ala319Val	missense_variant	10/13	ENST00000323578.13	NP_076436.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHID1	ENST00000323578.13 linkuse as main transcript	c.956C>T	p.Ala319Val	missense_variant	10/13	1	NM_023947.4	ENSP00000325055	P1	Q9BWS9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

250392

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135302

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1457488

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.1031C>T (p.A344V) alteration is located in exon 11 (coding exon 10) of the CHID1 gene. This alteration results from a C to T substitution at nucleotide position 1031, causing the alanine (A) at amino acid position 344 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

.;T;T;.;.;T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.91

D;D;.;D;.;.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.095

T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

.;L;L;.;.;L;.

MutationTaster

Benign

0.90

D;D;D;D;D;D;D;D

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.6

N;N;N;N;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.16

T;T;T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T;T;.

Polyphen

0.032

B;B;B;B;B;B;.

Vest4

0.38

MutPred

0.40

.;Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);.;.;Loss of loop (P = 0.0804);.;

MVP

0.20

MPC

0.26

ClinPred

0.045

GERP RS

2.3

Varity_R

0.041

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over