rs11594179

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016169.4(SUFU):c.*2668C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 233,262 control chromosomes in the GnomAD database, including 4,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2603 hom., cov: 32)

Exomes 𝑓: 0.19 ( 1739 hom. )

Consequence

SUFU
NM_016169.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.100

Publications

25 publications found

Variant links:

Genes affected

SUFU (HGNC:16466): (SUFU negative regulator of hedgehog signaling) The Hedgehog signaling pathway plays an important role in early human development. The pathway is a signaling cascade that plays a role in pattern formation and cellular proliferation during development. This gene encodes a negative regulator of the hedgehog signaling pathway. Defects in this gene are a cause of medulloblastoma. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

SUFU Gene-Disease associations (from GenCC):

medulloblastoma
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
nevoid basal cell carcinoma syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina, Genomics England PanelApp
basal cell nevus syndrome 2
Inheritance: AD Classification: STRONG Submitted by: G2P
ocular motor apraxia, Cogan type
Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox
Joubert syndrome 32
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Joubert syndrome
Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
apraxia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
ciliopathy
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

SUFU links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-102632823-C-T is Benign according to our data. Variant chr10-102632823-C-T is described in ClinVar as Benign. ClinVar VariationId is 298607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUFU	NM_016169.4 link	c.*2668C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8 link	c.*2668C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_016169.4	ENSP00000358918.4

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25952

AN:

152036

Hom.:

2603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0928

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.0470

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.204

GnomAD4 exome

AF:

0.192

AC:

15536

AN:

81108

Hom.:

1739

Cov.:

AF XY:

0.194

AC XY:

7233

AN XY:

37328

show subpopulations

African (AFR)

AF:

0.0951

AC:

371

AN:

3902

American (AMR)

AF:

0.148

AC:

371

AN:

2500

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1582

AN:

5124

East Asian (EAS)

AF:

0.0248

AC:

283

AN:

11414

South Asian (SAS)

AF:

0.126

AC:

AN:

700

European-Finnish (FIN)

AF:

0.221

AC:

AN:

Middle Eastern (MID)

AF:

0.175

AC:

AN:

492

European-Non Finnish (NFE)

AF:

0.226

AC:

11314

AN:

50130

Other (OTH)

AF:

0.210

AC:

1426

AN:

6778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

702

1404

2106

2808

3510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.171

AC:

25953

AN:

152154

Hom.:

2603

Cov.:

AF XY:

0.166

AC XY:

12320

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0926

AC:

3844

AN:

41518

American (AMR)

AF:

0.164

AC:

2500

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1033

AN:

3466

East Asian (EAS)

AF:

0.0471

AC:

244

AN:

5178

South Asian (SAS)

AF:

0.140

AC:

678

AN:

4828

European-Finnish (FIN)

AF:

0.175

AC:

1849

AN:

10564

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15014

AN:

67996

Other (OTH)

AF:

0.205

AC:

433

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1083

2166

3248

4331

5414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.209

Hom.:

6040

Bravo

AF:

0.167

Asia WGS

AF:

0.0920

AC:

322

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Medulloblastoma

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.9

(source)

DANN

Benign

0.49

PhyloP100

0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over