chr2-233264857-G-A

Variant names:

• chr2-233264857-G-A
• rs12994997
• NM_030803.7:c.390-35G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030803.7(ATG16L1):​c.390-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,610,478 control chromosomes in the GnomAD database, including 202,772 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15107 hom., cov: 32)
  • Exomes 𝑓: 0.50 (187665 hom.)
• Consequence: ATG16L1 NM_030803.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 70 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

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.390-35G>A		intron	N/A	NP_110430.5
	ATG16L1	NM_001363742.2		c.390-35G>A		intron	N/A	NP_001350671.1	E7EVC7
	ATG16L1	NM_017974.4		c.390-35G>A		intron	N/A	NP_060444.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG16L1	ENST00000392017.9	TSL:1 MANE Select	c.390-35G>A		intron	N/A	ENSP00000375872.4	Q676U5-1
	ATG16L1	ENST00000392020.8	TSL:1	c.390-35G>A		intron	N/A	ENSP00000375875.4	Q676U5-2
	ATG16L1	ENST00000347464.9	TSL:1	c.210-5145G>A		intron	N/A	ENSP00000318259.6	Q676U5-5

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66137 AN: 151902 Hom.: 15106 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.442

GnomAD2 exomes AF: 0.452 AC: 112742 AN: 249188 AF XY: 0.468

Gnomad AFR exome AF: 0.322

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: 0.501 AC: 730868 AN: 1458458 Hom.: 187665 Cov.: 43 AF XY: 0.504 AC XY: 365407 AN XY: 725420

African (AFR) AF: 0.317 AC: 10585 AN: 33416

American (AMR) AF: 0.252 AC: 11253 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 15924 AN: 26070

East Asian (EAS) AF: 0.278 AC: 11018 AN: 39654

South Asian (SAS) AF: 0.525 AC: 45199 AN: 86118

European-Finnish (FIN) AF: 0.442 AC: 23337 AN: 52836

Middle Eastern (MID) AF: 0.546 AC: 2562 AN: 4696

European-Non Finnish (NFE) AF: 0.524 AC: 581585 AN: 1110786

Other (OTH) AF: 0.488 AC: 29405 AN: 60198

GnomAD4 genome AF: 0.435 AC: 66136 AN: 152020 Hom.: 15107 Cov.: 32 AF XY: 0.430 AC XY: 31943 AN XY: 74306

African (AFR) AF: 0.319 AC: 13200 AN: 41436

American (AMR) AF: 0.353 AC: 5393 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2085 AN: 3470

East Asian (EAS) AF: 0.314 AC: 1629 AN: 5182

South Asian (SAS) AF: 0.509 AC: 2452 AN: 4816

European-Finnish (FIN) AF: 0.437 AC: 4607 AN: 10550

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35220 AN: 67972

Other (OTH) AF: 0.437 AC: 922 AN: 2110

Alfa AF: 0.469 Hom.: 33016

Bravo AF: 0.421

Asia WGS AF: 0.360 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.82
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12994997; hg19: chr2-234173503; COSMIC: COSV61464793; COSMIC: COSV61464793;