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rs2241880

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. 13/19 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

15

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O: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]

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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/exons MANE UniProt
ATG16L1NM_030803.7 linkuse as main transcriptc.898A>G p.Thr300Ala missense_variant 9/18 ENST00000392017.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATG16L1ENST00000392017.9 linkuse as main transcriptc.898A>G p.Thr300Ala missense_variant 9/181 NM_030803.7 P3Q676U5-1

Frequencies

GnomAD3 genomes
AF:
0.438
AC:
66455
AN:
151798
Hom.:
15197
Cov.:
32
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.:
36
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.:
32
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:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Feb 24, 2015- -
ATG16L1-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Inflammatory bowel disease 10, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMFeb 27, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.056
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.58
Cadd
Benign
0.62
Dann
Benign
0.71
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.034
N
MetaRNN
Benign
0.000019
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
P;P;P;P;P
PrimateAI
Benign
0.26
T
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
T
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.

Other links and lift over

dbSNP: rs2241880; hg19: chr2-234183368; COSMIC: COSV61464428; COSMIC: COSV61464428; API