chr7-65967580-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000181.4(GUSB):​c.1653+151A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000176 in 567,388 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: GUSB NM_000181.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: G2P, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUSB	NM_000181.4	MANE Select	c.1653+151A>T		intron	N/A	NP_000172.2
	GUSB	NM_001284290.2		c.1215+151A>T		intron	N/A	NP_001271219.1
	GUSB	NM_001293104.2		c.1083+151A>T		intron	N/A	NP_001280033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUSB	ENST00000304895.9	TSL:1 MANE Select	c.1653+151A>T		intron	N/A	ENSP00000302728.4
	GUSB	ENST00000461622.1	TSL:1	n.178+151A>T		intron	N/A
	GUSB	ENST00000421103.5	TSL:2	c.1215+151A>T		intron	N/A	ENSP00000391390.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000176 AC: 1 AN: 567388 Hom.: 0 AF XY: 0.00000325 AC XY: 1 AN XY: 307288

African (AFR) AF: 0.00 AC: 0 AN: 16350

American (AMR) AF: 0.00 AC: 0 AN: 35302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19476

East Asian (EAS) AF: 0.00 AC: 0 AN: 32046

South Asian (SAS) AF: 0.00 AC: 0 AN: 64344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2546

European-Non Finnish (NFE) AF: 0.00000301 AC: 1 AN: 332360

Other (OTH) AF: 0.00 AC: 0 AN: 30640

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.61
DANN	Benign	0.76
PhyloP100		-2.1

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;