chr2-233270016-G-T

Variant names:

• chr2-233270016-G-T
• rs115732365
• NM_030803.7:c.656G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_030803.7(ATG16L1):​c.656G>T​(p.Arg219Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 1,575,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R219Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: ATG16L1 NM_030803.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28
• Publications: 4 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25007114).
• BS2: High AC in GnomAdExome4 at 10 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG16L1	NM_030803.7	MANE Select	c.656G>T	p.Arg219Leu	missense	Exon 6 of 18	NP_110430.5
	ATG16L1	NM_001363742.2		c.656G>T	p.Arg219Leu	missense	Exon 6 of 19	NP_001350671.1	E7EVC7
	ATG16L1	NM_017974.4		c.656G>T	p.Arg219Leu	missense	Exon 6 of 17	NP_060444.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG16L1	ENST00000392017.9	TSL:1 MANE Select	c.656G>T	p.Arg219Leu	missense	Exon 6 of 18	ENSP00000375872.4	Q676U5-1
	ATG16L1	ENST00000392020.8	TSL:1	c.656G>T	p.Arg219Leu	missense	Exon 6 of 17	ENSP00000375875.4	Q676U5-2
	ATG16L1	ENST00000347464.9	TSL:1	c.224G>T	p.Arg75Leu	missense	Exon 3 of 14	ENSP00000318259.6	Q676U5-5

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151332 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000226 AC: 5 AN: 221458 AF XY: 0.0000166

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000702 AC: 10 AN: 1423698 Hom.: 0 Cov.: 34 AF XY: 0.00000424 AC XY: 3 AN XY: 707932

African (AFR) AF: 0.00 AC: 0 AN: 30872

American (AMR) AF: 0.000266 AC: 10 AN: 37530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25146

East Asian (EAS) AF: 0.00 AC: 0 AN: 38080

South Asian (SAS) AF: 0.00 AC: 0 AN: 78714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096464

Other (OTH) AF: 0.00 AC: 0 AN: 58456

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151332 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73848

African (AFR) AF: 0.00 AC: 0 AN: 41172

American (AMR) AF: 0.0000658 AC: 1 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67898

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 720

Bravo AF: 0.0000264

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.087
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.086	T
Polyphen		0.69	P
Vest4		0.62
MutPred		0.43		Loss of MoRF binding (P = 0.0061)
MVP		0.51
MPC		1.1
ClinPred		0.62	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.18
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs115732365; hg19: chr2-234178662;