rs4905480

Positions:

• chr14-96293516-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018036.7(ATG2B):​c.5427-1418T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,062 control chromosomes in the GnomAD database, including 9,876 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 0.35 (9876 hom., cov: 32)
• Consequence: ATG2B NM_018036.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG2B	NM_018036.7	c.5427-1418T>G		intron_variant		ENST00000359933.6	NP_060506.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG2B	ENST00000359933.6	c.5427-1418T>G		intron_variant		5	NM_018036.7	ENSP00000353010.4
ATG2B	ENST00000261834.9	n.1413-1418T>G		intron_variant		2
ATG2B	ENST00000554151.1	n.101-302T>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52879 AN: 151942 Hom.: 9877 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.348 AC: 52892 AN: 152062 Hom.: 9876 Cov.: 32 AF XY: 0.342 AC XY: 25409 AN XY: 74324

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.326

Alfa AF: 0.402 Hom.: 25842

Bravo AF: 0.350

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.30
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs4905480; hg19: chr14-96759853;