chr2-233274722-A-G

Variant names:

• chr2-233274722-A-G
• rs2241880
• NM_030803.7:c.898A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001363742.2(ATG16L1):​c.949A>G​(p.Thr317Ala) 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. 15/21 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_001363742.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.448
• Publications: 681 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.8645105E-5).
• BP6: Variant 2-233274722-A-G is Benign according to our data. Variant chr2-233274722-A-G is described in ClinVar as Benign. ClinVar VariationId is 1130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363742.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG16L1	NM_030803.7	MANE Select	c.898A>G	p.Thr300Ala	missense	Exon 9 of 18	NP_110430.5
	ATG16L1	NM_001363742.2		c.949A>G	p.Thr317Ala	missense	Exon 10 of 19	NP_001350671.1
	ATG16L1	NM_017974.4		c.841A>G	p.Thr281Ala	missense	Exon 8 of 17	NP_060444.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG16L1	ENST00000392017.9	TSL:1 MANE Select	c.898A>G	p.Thr300Ala	missense	Exon 9 of 18	ENSP00000375872.4
	ATG16L1	ENST00000392020.8	TSL:1	c.841A>G	p.Thr281Ala	missense	Exon 8 of 17	ENSP00000375875.4
	ATG16L1	ENST00000347464.9	TSL:1	c.409A>G	p.Thr137Ala	missense	Exon 5 of 14	ENSP00000318259.6

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66455 AN: 151798 Hom.: 15197 Cov.: 32

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

GnomAD2 exomes AF: 0.453 AC: 113606 AN: 250652 AF XY: 0.469

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 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

African (AFR) AF: 0.320 AC: 10689 AN: 33378

American (AMR) AF: 0.252 AC: 11259 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 15917 AN: 26056

East Asian (EAS) AF: 0.278 AC: 11010 AN: 39634

South Asian (SAS) AF: 0.526 AC: 45241 AN: 86068

European-Finnish (FIN) AF: 0.442 AC: 23552 AN: 53342

Middle Eastern (MID) AF: 0.526 AC: 3024 AN: 5748

European-Non Finnish (NFE) AF: 0.524 AC: 580781 AN: 1108094

Other (OTH) AF: 0.489 AC: 29442 AN: 60230

GnomAD4 genome AF: 0.437 AC: 66454 AN: 151916 Hom.: 15195 Cov.: 32 AF XY: 0.432 AC XY: 32071 AN XY: 74208

African (AFR) AF: 0.324 AC: 13436 AN: 41424

American (AMR) AF: 0.354 AC: 5415 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2084 AN: 3468

East Asian (EAS) AF: 0.314 AC: 1623 AN: 5166

South Asian (SAS) AF: 0.511 AC: 2453 AN: 4802

European-Finnish (FIN) AF: 0.438 AC: 4605 AN: 10522

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35287 AN: 67950

Other (OTH) AF: 0.438 AC: 921 AN: 2102

Alfa AF: 0.494 Hom.: 89219

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	ATG16L1-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	-	Inflammatory bowel disease 10, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.034	N
MetaRNN	Benign	0.000019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.81	N
PhyloP100		-0.45
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.072
Sift	Benign	0.61	T
Sift4G	Benign	1.0	T
Polyphen		0.0	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
Mutation Taster		=82/18	polymorphism (auto)

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

Other links and lift over

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