rs781143

Variant names:

• chr7-65974892-G-C
• rs781143
• NM_000181.4:c.1065+27C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-65974892-G-C
• chr7-65974892-G-A
• chr7-65974892-G-T

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.1065+27C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,609,890 control chromosomes in the GnomAD database, including 255,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21189 hom., cov: 31)
  • Exomes 𝑓: 0.56 (234316 hom.)
• Consequence: GUSB NM_000181.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.831
• Publications: 11 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=-0.84).
• BP6: Variant 7-65974892-G-C is Benign according to our data. Variant chr7-65974892-G-C is described in ClinVar as Benign. ClinVar VariationId is 92583.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.1065+27C>G		intron	N/A	NP_000172.2	P08236-1
	GUSB	NM_001284290.2		c.627+27C>G		intron	N/A	NP_001271219.1	P08236-3
	GUSB	NM_001293104.2		c.495+27C>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.1065+27C>G		intron	N/A	ENSP00000302728.4	P08236-1
	GUSB	ENST00000864783.1		c.1149+27C>G		intron	N/A	ENSP00000534842.1
	GUSB	ENST00000864792.1		c.1128+27C>G		intron	N/A	ENSP00000534851.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78409 AN: 151862 Hom.: 21178 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.530

GnomAD2 exomes AF: 0.578 AC: 144984 AN: 250980 AF XY: 0.582

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.552

Gnomad ASJ exome AF: 0.635

Gnomad EAS exome AF: 0.806

Gnomad FIN exome AF: 0.624

Gnomad NFE exome AF: 0.554

Gnomad OTH exome AF: 0.577

GnomAD4 exome AF: 0.562 AC: 819768 AN: 1457910 Hom.: 234316 Cov.: 34 AF XY: 0.565 AC XY: 410106 AN XY: 725412

African (AFR) AF: 0.359 AC: 11983 AN: 33396

American (AMR) AF: 0.546 AC: 24402 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 16480 AN: 26106

East Asian (EAS) AF: 0.862 AC: 34203 AN: 39686

South Asian (SAS) AF: 0.614 AC: 52886 AN: 86082

European-Finnish (FIN) AF: 0.622 AC: 33191 AN: 53402

Middle Eastern (MID) AF: 0.607 AC: 3101 AN: 5110

European-Non Finnish (NFE) AF: 0.550 AC: 609585 AN: 1109214

Other (OTH) AF: 0.564 AC: 33937 AN: 60204

GnomAD4 genome AF: 0.516 AC: 78456 AN: 151980 Hom.: 21189 Cov.: 31 AF XY: 0.522 AC XY: 38767 AN XY: 74282

African (AFR) AF: 0.371 AC: 15359 AN: 41442

American (AMR) AF: 0.528 AC: 8064 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2156 AN: 3470

East Asian (EAS) AF: 0.807 AC: 4159 AN: 5152

South Asian (SAS) AF: 0.637 AC: 3070 AN: 4818

European-Finnish (FIN) AF: 0.612 AC: 6459 AN: 10562

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.549 AC: 37303 AN: 67954

Other (OTH) AF: 0.534 AC: 1125 AN: 2108

Alfa AF: 0.486 Hom.: 2691

Bravo AF: 0.506

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.36
PhyloP100		0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs781143; hg19: chr7-65439879; COSMIC: COSV59221579; COSMIC: COSV59221579;