chr2-233264930-C-T

Variant names:

• chr2-233264930-C-T
• rs774397068
• NM_030803.7:c.428C>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.428C>T​(p.Thr143Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ATG16L1 NM_030803.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71
• Publications: 3 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=0.21510074).
• BS2: High AC in GnomAdExome4 at 8 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.428C>T	p.Thr143Met	missense	Exon 5 of 18	NP_110430.5
	ATG16L1	NM_001363742.2		c.428C>T	p.Thr143Met	missense	Exon 5 of 19	NP_001350671.1	E7EVC7
	ATG16L1	NM_017974.4		c.428C>T	p.Thr143Met	missense	Exon 5 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.428C>T	p.Thr143Met	missense	Exon 5 of 18	ENSP00000375872.4	Q676U5-1
	ATG16L1	ENST00000392020.8	TSL:1	c.428C>T	p.Thr143Met	missense	Exon 5 of 17	ENSP00000375875.4	Q676U5-2
	ATG16L1	ENST00000347464.9	TSL:1	c.210-5072C>T		intron	N/A	ENSP00000318259.6	Q676U5-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251278 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461720 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727170

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1111890

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.7
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.092
Sift	Uncertain	0.029	D
Sift4G	Benign	0.079	T
Polyphen		0.99	D
Vest4		0.32
MutPred		0.43		Loss of phosphorylation at T143 (P = 0.1177)
MVP		0.55
MPC		1.4
ClinPred		0.47	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.092
Mutation Taster		=92/8	polymorphism

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: rs774397068; hg19: chr2-234173576; COSMIC: COSV61465196; COSMIC: COSV61465196;