rs3759601

Variant names:

• chr14-96311131-G-C
• rs3759601
• NM_018036.7:c.4147C>G

Variant summary

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

The NM_018036.7(ATG2B):​c.4147C>G​(p.Gln1383Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,610,334 control chromosomes in the GnomAD database, including 131,674 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 0.32 (9152 hom., cov: 32)
  • Exomes 𝑓: 0.40 (122522 hom.)
• Consequence: ATG2B NM_018036.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.13
• Publications: 52 publications found

Genes affected

ATG2B (HGNC:20187): (autophagy related 2B) This gene encodes a protein required for autophagy. The encoded protein is involved in autophagosome formation. A germline duplication of a region that includes this gene is associated with predisposition to myeloid malignancies. [provided by RefSeq, Jul 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022884905).
• BP6: Variant 14-96311131-G-C is Benign according to our data. Variant chr14-96311131-G-C is described in ClinVar as Benign. ClinVar VariationId is 1269383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018036.7. 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
	ATG2B	NM_018036.7	MANE Select	c.4147C>G	p.Gln1383Glu	missense	Exon 28 of 42	NP_060506.6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG2B	ENST00000359933.6	TSL:5 MANE Select	c.4147C>G	p.Gln1383Glu	missense	Exon 28 of 42	ENSP00000353010.4	Q96BY7
	ATG2B	ENST00000938845.1		c.4147C>G	p.Gln1383Glu	missense	Exon 28 of 42	ENSP00000608904.1
	ATG2B	ENST00000261834.9	TSL:2	n.133C>G		non_coding_transcript_exon	Exon 1 of 14

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49310 AN: 151870 Hom.: 9153 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.314

GnomAD2 exomes AF: 0.357 AC: 88892 AN: 248692 AF XY: 0.355

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.435

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.201

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.425

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.402 AC: 586515 AN: 1458346 Hom.: 122522 Cov.: 35 AF XY: 0.398 AC XY: 288430 AN XY: 725468

African (AFR) AF: 0.145 AC: 4827 AN: 33334

American (AMR) AF: 0.432 AC: 19126 AN: 44254

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8694 AN: 25972

East Asian (EAS) AF: 0.198 AC: 7833 AN: 39626

South Asian (SAS) AF: 0.244 AC: 20909 AN: 85862

European-Finnish (FIN) AF: 0.361 AC: 19239 AN: 53362

Middle Eastern (MID) AF: 0.289 AC: 1660 AN: 5750

European-Non Finnish (NFE) AF: 0.435 AC: 482574 AN: 1109954

Other (OTH) AF: 0.359 AC: 21653 AN: 60232

GnomAD4 genome AF: 0.324 AC: 49319 AN: 151988 Hom.: 9152 Cov.: 32 AF XY: 0.320 AC XY: 23766 AN XY: 74276

African (AFR) AF: 0.159 AC: 6577 AN: 41474

American (AMR) AF: 0.395 AC: 6035 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1111 AN: 3466

East Asian (EAS) AF: 0.199 AC: 1027 AN: 5156

South Asian (SAS) AF: 0.233 AC: 1120 AN: 4816

European-Finnish (FIN) AF: 0.348 AC: 3674 AN: 10552

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28750 AN: 67950

Other (OTH) AF: 0.310 AC: 653 AN: 2108

Alfa AF: 0.394 Hom.: 9221

Bravo AF: 0.323

TwinsUK AF: 0.460 AC: 1707

ALSPAC AF: 0.442 AC: 1704

ESP6500AA AF: 0.171 AC: 755

ESP6500EA AF: 0.423 AC: 3634

ExAC AF: 0.353 AC: 42859

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.20
DEOGEN2	Benign	0.00039	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.1
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.024
MPC		0.18
ClinPred		0.0042	T
GERP RS		2.5
Varity_R		0.038
gMVP		0.13
Mutation Taster		=98/2	polymorphism (auto)

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: rs3759601; hg19: chr14-96777468; COSMIC: COSV55890059;