rs1061361

Variant names:

• chr7-65964372-G-A
• rs1061361
• NM_000181.4:c.1740C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-65964372-G-A
• chr7-65964372-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000181.4(GUSB):​c.1740C>T​(p.Tyr580Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,610,650 control chromosomes in the GnomAD database, including 11,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1084 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10297 hom.)
• Consequence: GUSB NM_000181.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.649
• Publications: 21 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 7-65964372-G-A is Benign according to our data. Variant chr7-65964372-G-A is described in ClinVar as Benign. ClinVar VariationId is 92587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.649 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUSB	NM_000181.4	MANE Select	c.1740C>T	p.Tyr580Tyr	synonymous	Exon 11 of 12	NP_000172.2
	GUSB	NM_001284290.2		c.1302C>T	p.Tyr434Tyr	synonymous	Exon 9 of 10	NP_001271219.1
	GUSB	NM_001293104.2		c.1170C>T	p.Tyr390Tyr	synonymous	Exon 10 of 11	NP_001280033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUSB	ENST00000304895.9	TSL:1 MANE Select	c.1740C>T	p.Tyr580Tyr	synonymous	Exon 11 of 12	ENSP00000302728.4
	GUSB	ENST00000461622.1	TSL:1	n.265C>T		non_coding_transcript_exon	Exon 2 of 2
	GUSB	ENST00000421103.5	TSL:2	c.1302C>T	p.Tyr434Tyr	synonymous	Exon 9 of 10	ENSP00000391390.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16677 AN: 152052 Hom.: 1083 Cov.: 32

Gnomad AFR AF: 0.0831

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0619

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.132

GnomAD2 exomes AF: 0.132 AC: 33123 AN: 251418 AF XY: 0.134

Gnomad AFR exome AF: 0.0809

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.179

Gnomad EAS exome AF: 0.165

Gnomad FIN exome AF: 0.0669

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.111 AC: 162161 AN: 1458480 Hom.: 10297 Cov.: 31 AF XY: 0.114 AC XY: 82640 AN XY: 725602

African (AFR) AF: 0.0822 AC: 2744 AN: 33388

American (AMR) AF: 0.194 AC: 8690 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 4546 AN: 26118

East Asian (EAS) AF: 0.162 AC: 6447 AN: 39682

South Asian (SAS) AF: 0.187 AC: 16082 AN: 86132

European-Finnish (FIN) AF: 0.0708 AC: 3781 AN: 53418

Middle Eastern (MID) AF: 0.222 AC: 918 AN: 4138

European-Non Finnish (NFE) AF: 0.101 AC: 111793 AN: 1110722

Other (OTH) AF: 0.119 AC: 7160 AN: 60164

GnomAD4 genome AF: 0.110 AC: 16682 AN: 152170 Hom.: 1084 Cov.: 32 AF XY: 0.112 AC XY: 8329 AN XY: 74374

African (AFR) AF: 0.0830 AC: 3447 AN: 41514

American (AMR) AF: 0.168 AC: 2567 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3472

East Asian (EAS) AF: 0.158 AC: 817 AN: 5182

South Asian (SAS) AF: 0.195 AC: 942 AN: 4822

European-Finnish (FIN) AF: 0.0619 AC: 655 AN: 10586

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7135 AN: 67998

Other (OTH) AF: 0.130 AC: 274 AN: 2110

Alfa AF: 0.119 Hom.: 372

Bravo AF: 0.117

Asia WGS AF: 0.149 AC: 523 AN: 3478

EpiCase AF: 0.126

EpiControl AF: 0.121

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Mucopolysaccharidosis type 7 (3)
-	-	3	not provided (3)
-	-	3	not specified (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.28
DANN	Benign	0.72
PhyloP100		-0.65
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: rs1061361; hg19: chr7-65429359; COSMIC: COSV59223092; COSMIC: COSV59223092;