rs12994997

Positions:

• chr2-233264857-G-A
• chr2-233264857-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG16L1	NM_030803.7	c.390-35G>A		intron_variant		ENST00000392017.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG16L1	ENST00000392017.9	c.390-35G>A		intron_variant		1	NM_030803.7	P3

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

GnomAD3 exomes AF: 0.452 AC: 112742 AN: 249188 Hom.: 27300 AF XY: 0.468 AC XY: 63036 AN XY: 134726

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 SAS exome AF: 0.520

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

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.252

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.278

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.442

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.488

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

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.437

Alfa AF: 0.402 Hom.: 3300

Bravo AF: 0.421

Asia WGS AF: 0.360 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs12994997; hg19: chr2-234173503; COSMIC: COSV61464793; COSMIC: COSV61464793;