rs2271101

Positions:

• chr4-177438565-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000027.4(AGA):​c.507+180T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,966 control chromosomes in the GnomAD database, including 15,461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (15461 hom., cov: 32)
• Consequence: AGA NM_000027.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.891

Genes affected

AGA (HGNC:318): (aspartylglucosaminidase) This gene encodes a member of the N-terminal nucleophile (Ntn) hydrolase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta chains that comprise the mature enzyme. This enzyme is involved in the catabolism of N-linked oligosaccharides of glycoproteins. It cleaves asparagine from N-acetylglucosamines as one of the final steps in the lysosomal breakdown of glycoproteins. Mutations in this gene are associated with the lysosomal storage disease aspartylglycosaminuria that results in progressive neurodegeneration. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is subject to proteolytic processing. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 4-177438565-A-G is Benign according to our data. Variant chr4-177438565-A-G is described in ClinVar as [Benign]. Clinvar id is 1254787.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGA	NM_000027.4	c.507+180T>C		intron_variant		ENST00000264595.7
AGA	NM_001171988.2	c.507+180T>C		intron_variant
AGA	XM_047449722.1	c.507+180T>C		intron_variant
AGA	NR_033655.2	n.569+180T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGA	ENST00000264595.7	c.507+180T>C		intron_variant		1	NM_000027.4	P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68058 AN: 151848 Hom.: 15429 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.448 AC: 68136 AN: 151966 Hom.: 15461 Cov.: 32 AF XY: 0.444 AC XY: 32958 AN XY: 74246

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.419

Alfa AF: 0.464 Hom.: 4442

Bravo AF: 0.450

Asia WGS AF: 0.332 AC: 1157 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.54

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: rs2271101; hg19: chr4-178359719;