chr2-233274722-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030803.7(ATG16L1):c.898A>G(p.Thr300Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,609,114 control chromosomes in the GnomAD database, including 203,415 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 0.44 ( 15195 hom., cov: 32)

Exomes 𝑓: 0.50 ( 188220 hom. )

Consequence

ATG16L1
NM_030803.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.448

Variant links:

Genes affected

ATG16L1 (HGNC:21498): (autophagy related 16 like 1) The protein encoded by this gene is part of a large protein complex that is necessary for autophagy, the major process by which intracellular components are targeted to lysosomes for degradation. Defects in this gene are a cause of susceptibility to inflammatory bowel disease type 10 (IBD10). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2010]

ATG16L1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8645105E-5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG16L1	NM_030803.7 link	c.898A>G	p.Thr300Ala	missense_variant	Exon 9 of 18	ENST00000392017.9	NP_110430.5	Q676U5-1Q17RG0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG16L1	ENST00000392017.9 link	c.898A>G	p.Thr300Ala	missense_variant	Exon 9 of 18	1	NM_030803.7	ENSP00000375872.4		Q676U5-1

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66455

AN:

151798

Hom.:

15197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.528

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.519

Gnomad OTH

AF:

0.443

GnomAD3 exomes

AF:

0.453

AC:

113606

AN:

250652

Hom.:

27569

AF XY:

0.469

AC XY:

63500

AN XY:

135462

show subpopulations

Gnomad AFR exome

AF:

0.327

Gnomad AMR exome

AF:

0.238

Gnomad ASJ exome

AF:

0.617

Gnomad EAS exome

AF:

0.333

Gnomad SAS exome

AF:

0.521

Gnomad FIN exome

AF:

0.449

Gnomad NFE exome

AF:

0.523

Gnomad OTH exome

AF:

0.475

GnomAD4 exome

AF:

0.502

AC:

730915

AN:

1457198

Hom.:

188220

Cov.:

AF XY:

0.504

AC XY:

365648

AN XY:

725132

show subpopulations

Gnomad4 AFR exome

AF:

0.320

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.611

Gnomad4 EAS exome

AF:

0.278

Gnomad4 SAS exome

AF:

0.526

Gnomad4 FIN exome

AF:

0.442

Gnomad4 NFE exome

AF:

0.524

Gnomad4 OTH exome

AF:

0.489

GnomAD4 genome

AF:

0.437

AC:

66454

AN:

151916

Hom.:

15195

Cov.:

AF XY:

0.432

AC XY:

32071

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.324

Gnomad4 AMR

AF:

0.354

Gnomad4 ASJ

AF:

0.601

Gnomad4 EAS

AF:

0.314

Gnomad4 SAS

AF:

0.511

Gnomad4 FIN

AF:

0.438

Gnomad4 NFE

AF:

0.519

Gnomad4 OTH

AF:

0.438

Alfa

AF:

0.506

Hom.:

49100

Bravo

AF:

0.423

TwinsUK

AF:

0.524

AC:

1942

ALSPAC

AF:

0.520

AC:

2005

ESP6500AA

AF:

0.324

AC:

1428

ESP6500EA

AF:

0.524

AC:

4506

ExAC

AF:

0.457

AC:

55525

Asia WGS

AF:

0.359

AC:

1250

AN:

3478

EpiCase

AF:

0.531

EpiControl

AF:

0.522

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 24, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ATG16L1-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Inflammatory bowel disease 10, susceptibility to

Other:1

Feb 27, 2014

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.62

DANN

Benign

0.71

DEOGEN2

Benign

0.017

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

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.034

MetaRNN

Benign

0.000019

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

.;N;.;.;.;.;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.10

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

REVEL

Benign

0.072

Sift

Benign

0.61

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

Sift4G

Benign

1.0

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

Polyphen

0.0, 0.0010

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

Vest4

0.049

MPC

0.56

ClinPred

0.017

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.026

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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