Genetic Variant ATG16L1:p.Arg219Gln (chr2-233270016-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_030803.7(ATG16L1):c.656G>A(p.Arg219Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000301 in 1,575,136 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

ATG16L1
NM_030803.7 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.28

Publications

4 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008304119).

BP6

Variant 2-233270016-G-A is Benign according to our data. Variant chr2-233270016-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3053014.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 212 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030803.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATG16L1	NM_030803.7	MANE Select	c.656G>A	p.Arg219Gln	missense	Exon 6 of 18	NP_110430.5
ATG16L1	NM_001363742.2		c.656G>A	p.Arg219Gln	missense	Exon 6 of 19	NP_001350671.1	E7EVC7
ATG16L1	NM_017974.4		c.656G>A	p.Arg219Gln	missense	Exon 6 of 17	NP_060444.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATG16L1	ENST00000392017.9	TSL:1 MANE Select	c.656G>A	p.Arg219Gln	missense	Exon 6 of 18	ENSP00000375872.4	Q676U5-1
ATG16L1	ENST00000392020.8	TSL:1	c.656G>A	p.Arg219Gln	missense	Exon 6 of 17	ENSP00000375875.4	Q676U5-2
ATG16L1	ENST00000347464.9	TSL:1	c.224G>A	p.Arg75Gln	missense	Exon 3 of 14	ENSP00000318259.6	Q676U5-5

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

212

AN:

151332

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00491

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000438

AC:

AN:

221458

AF XY:

0.000340

show subpopulations

Gnomad AFR exome

AF:

0.00552

Gnomad AMR exome

AF:

0.000185

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000766

Gnomad OTH exome

AF:

0.000394

GnomAD4 exome

AF:

0.000184

AC:

262

AN:

1423696

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

121

AN XY:

707932

show subpopulations

African (AFR)

AF:

0.00502

AC:

155

AN:

30872

American (AMR)

AF:

0.000133

AC:

AN:

37530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25146

East Asian (EAS)

AF:

0.00

AC:

AN:

38080

South Asian (SAS)

AF:

0.0000381

AC:

AN:

78714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

0.0000730

AC:

AN:

1096464

Other (OTH)

AF:

0.000325

AC:

AN:

58456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00140

AC:

212

AN:

151440

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

73966

show subpopulations

African (AFR)

AF:

0.00489

AC:

202

AN:

41292

American (AMR)

AF:

0.000263

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67890

Other (OTH)

AF:

0.00190

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00614

Hom.:

720

Bravo

AF:

0.00154

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000486

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ATG16L1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.0075

MetaRNN

Benign

0.0083

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

PhyloP100

3.3

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.95

REVEL

Benign

0.039

Sift

Benign

0.099

Sift4G

Benign

0.14

Polyphen

0.71

Vest4

0.46

MVP

0.59

MPC

0.67

ClinPred

0.0090

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.099

gMVP

0.11

Mutation Taster

=78/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over