rs2271100

Positions:

• chr4-177438525-T-C

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+220A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,132 control chromosomes in the GnomAD database, including 3,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3087 hom., cov: 32)
• Consequence: AGA NM_000027.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49

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=-0.9).
• BP6: Variant 4-177438525-T-C is Benign according to our data. Variant chr4-177438525-T-C is described in ClinVar as [Benign]. Clinvar id is 1238985.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGA	NM_000027.4	c.507+220A>G		intron_variant		ENST00000264595.7	NP_000018.2
AGA	NM_001171988.2	c.507+220A>G		intron_variant			NP_001165459.1
AGA	XM_047449722.1	c.507+220A>G		intron_variant			XP_047305678.1
AGA	NR_033655.2	n.569+220A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGA	ENST00000264595.7	c.507+220A>G		intron_variant		1	NM_000027.4	ENSP00000264595	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29181 AN: 152014 Hom.: 3090 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.192 AC: 29174 AN: 152132 Hom.: 3087 Cov.: 32 AF XY: 0.190 AC XY: 14158 AN XY: 74362

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.234

Alfa AF: 0.228 Hom.: 5571

Bravo AF: 0.187

Asia WGS AF: 0.148 AC: 516 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	-0.90
CADD	Benign	0.020
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: rs2271100; hg19: chr4-178359679;