rs2274351

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_016169.4(SUFU):c.182+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,613,042 control chromosomes in the GnomAD database, including 219,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17119 hom., cov: 32)

Exomes 𝑓: 0.52 ( 202847 hom. )

Consequence

SUFU
NM_016169.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.175

Publications

40 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
nevoid basal cell carcinoma syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Genomics England PanelApp, Orphanet
basal cell nevus syndrome 2
Inheritance: AD Classification: STRONG Submitted by: G2P
neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
ocular motor apraxia, Cogan type
Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox
Joubert syndrome 32
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
Joubert syndrome
Inheritance: AD, AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 10-102504350-C-T is Benign according to our data. Variant chr10-102504350-C-T is described in ClinVar as Benign. ClinVar VariationId is 260689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016169.4. 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
	SUFU	NM_016169.4	MANE Select	c.182+16C>T		intron	N/A	NP_057253.2
	SUFU	NM_001178133.2		c.182+16C>T		intron	N/A	NP_001171604.1	Q9UMX1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SUFU	ENST00000369902.8	TSL:1 MANE Select	c.182+16C>T	intron	N/A	ENSP00000358918.4	Q9UMX1-1
SUFU	ENST00000423559.2	TSL:1	c.182+16C>T	intron	N/A	ENSP00000411597.2	Q9UMX1-3
SUFU	ENST00000369899.6	TSL:1	c.182+16C>T	intron	N/A	ENSP00000358915.2	Q9UMX1-2

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

70016

AN:

151774

Hom.:

17115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.521

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.547

Gnomad OTH

AF:

0.500

GnomAD2 exomes

AF:

0.476

AC:

117166

AN:

246288

AF XY:

0.489

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.662

Gnomad EAS exome

AF:

0.322

Gnomad FIN exome

AF:

0.520

Gnomad NFE exome

AF:

0.548

Gnomad OTH exome

AF:

0.526

GnomAD4 exome

AF:

0.521

AC:

761462

AN:

1461150

Hom.:

202847

Cov.:

AF XY:

0.523

AC XY:

379841

AN XY:

726814

show subpopulations

African (AFR)

AF:

0.310

AC:

10369

AN:

33462

American (AMR)

AF:

0.313

AC:

13985

AN:

44614

Ashkenazi Jewish (ASJ)

AF:

0.665

AC:

17371

AN:

26124

East Asian (EAS)

AF:

0.267

AC:

10584

AN:

39674

South Asian (SAS)

AF:

0.486

AC:

41930

AN:

86206

European-Finnish (FIN)

AF:

0.523

AC:

27865

AN:

53268

Middle Eastern (MID)

AF:

0.591

AC:

3409

AN:

5766

European-Non Finnish (NFE)

AF:

0.544

AC:

604277

AN:

1111656

Other (OTH)

AF:

0.525

AC:

31672

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

19527

39055

58582

78110

97637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16834

33668

50502

67336

84170

<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:

0.461

AC:

70038

AN:

151892

Hom.:

17119

Cov.:

AF XY:

0.458

AC XY:

33956

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.318

AC:

13150

AN:

41400

American (AMR)

AF:

0.411

AC:

6279

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

2344

AN:

3468

East Asian (EAS)

AF:

0.321

AC:

1654

AN:

5148

South Asian (SAS)

AF:

0.487

AC:

2350

AN:

4824

European-Finnish (FIN)

AF:

0.521

AC:

5486

AN:

10530

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.547

AC:

37166

AN:

67942

Other (OTH)

AF:

0.500

AC:

1054

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1874

3748

5621

7495

9369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.513

Hom.:

58472

Bravo

AF:

0.442

Asia WGS

AF:

0.385

AC:

1341

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (3)

Familial meningioma (1)

Gorlin syndrome (1)

Gorlin syndrome;C0025149:Medulloblastoma (1)

Joubert syndrome 32 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

-0.17

PromoterAI

0.018

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over