7-65967580-T-C

Variant names:

• chr7-65967580-T-C
• rs1880555
• NM_000181.4:c.1653+151A>G

Variant summary

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

The NM_000181.4(GUSB):​c.1653+151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 718,606 control chromosomes in the GnomAD database, including 118,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20730 hom., cov: 32)
  • Exomes 𝑓: 0.58 (97915 hom.)
• Consequence: GUSB NM_000181.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.05
• Publications: 4 publications found

Genes affected

GUSB (HGNC:4696): (glucuronidase beta) This gene encodes a hydrolase that degrades glycosaminoglycans, including heparan sulfate, dermatan sulfate, and chondroitin-4,6-sulfate. The enzyme forms a homotetramer that is localized to the lysosome. Mutations in this gene result in mucopolysaccharidosis type VII. Alternative splicing results in multiple transcript variants. There are many pseudogenes of this locus in the human genome.[provided by RefSeq, May 2014]

GUSB Gene-Disease associations (from GenCC):

• mucopolysaccharidosis type 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-65967580-T-C is Benign according to our data. Variant chr7-65967580-T-C is described in ClinVar as Benign. ClinVar VariationId is 528232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000181.4. 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
	GUSB	NM_000181.4	MANE Select	c.1653+151A>G		intron	N/A	NP_000172.2	P08236-1
	GUSB	NM_001284290.2		c.1215+151A>G		intron	N/A	NP_001271219.1	P08236-3
	GUSB	NM_001293104.2		c.1083+151A>G		intron	N/A	NP_001280033.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUSB	ENST00000304895.9	TSL:1 MANE Select	c.1653+151A>G		intron	N/A	ENSP00000302728.4	P08236-1
	GUSB	ENST00000461622.1	TSL:1	n.178+151A>G		intron	N/A
	GUSB	ENST00000864783.1		c.1737+151A>G		intron	N/A	ENSP00000534842.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77219 AN: 151906 Hom.: 20718 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.580 AC: 328406 AN: 566582 Hom.: 97915 AF XY: 0.582 AC XY: 178612 AN XY: 306878

African (AFR) AF: 0.337 AC: 5511 AN: 16336

American (AMR) AF: 0.543 AC: 19152 AN: 35264

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 12294 AN: 19460

East Asian (EAS) AF: 0.872 AC: 27935 AN: 32024

South Asian (SAS) AF: 0.618 AC: 39748 AN: 64322

European-Finnish (FIN) AF: 0.619 AC: 21201 AN: 34238

Middle Eastern (MID) AF: 0.606 AC: 1538 AN: 2538

European-Non Finnish (NFE) AF: 0.554 AC: 183782 AN: 331836

Other (OTH) AF: 0.564 AC: 17245 AN: 30564

GnomAD4 genome AF: 0.508 AC: 77265 AN: 152024 Hom.: 20730 Cov.: 32 AF XY: 0.514 AC XY: 38173 AN XY: 74290

African (AFR) AF: 0.343 AC: 14206 AN: 41464

American (AMR) AF: 0.523 AC: 7988 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2144 AN: 3470

East Asian (EAS) AF: 0.808 AC: 4161 AN: 5152

South Asian (SAS) AF: 0.638 AC: 3073 AN: 4814

European-Finnish (FIN) AF: 0.612 AC: 6458 AN: 10560

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37364 AN: 67988

Other (OTH) AF: 0.525 AC: 1107 AN: 2110

Alfa AF: 0.516 Hom.: 2713

Bravo AF: 0.497

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Mucopolysaccharidosis type 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.59
PhyloP100		-2.1
Mutation Taster		=100/0	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: rs1880555; hg19: chr7-65432567;