Variant rs12414407 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016169.4(SUFU):c.1365+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,609,952 control chromosomes in the GnomAD database, including 346,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35758 hom., cov: 34)

Exomes 𝑓: 0.65 ( 310627 hom. )

Consequence

SUFU
NM_016169.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.452

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-102627262-T-C is Benign according to our data. Variant chr10-102627262-T-C is described in ClinVar as [Benign]. Clinvar id is 260688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102627262-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUFU	NM_016169.4 link	c.1365+19T>C		intron_variant	Intron 11 of 11	ENST00000369902.8	NP_057253.2	Q9UMX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8 link	c.1365+19T>C		intron_variant	Intron 11 of 11	1	NM_016169.4	ENSP00000358918.4		Q9UMX1-1

Frequencies

GnomAD3 genomes

AF:

0.683

AC:

103853

AN:

152102

Hom.:

35723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.752

Gnomad AMI

AF:

0.599

Gnomad AMR

AF:

0.634

Gnomad ASJ

AF:

0.701

Gnomad EAS

AF:

0.748

Gnomad SAS

AF:

0.711

Gnomad FIN

AF:

0.607

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.656

Gnomad OTH

AF:

0.702

GnomAD3 exomes

AF:

0.659

AC:

165628

AN:

251454

Hom.:

55054

AF XY:

0.662

AC XY:

89918

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.754

Gnomad AMR exome

AF:

0.578

Gnomad ASJ exome

AF:

0.689

Gnomad EAS exome

AF:

0.745

Gnomad SAS exome

AF:

0.714

Gnomad FIN exome

AF:

0.609

Gnomad NFE exome

AF:

0.647

Gnomad OTH exome

AF:

0.659

GnomAD4 exome

AF:

0.651

AC:

949428

AN:

1457730

Hom.:

310627

Cov.:

AF XY:

0.654

AC XY:

474177

AN XY:

725372

show subpopulations

Gnomad4 AFR exome

AF:

0.760

Gnomad4 AMR exome

AF:

0.587

Gnomad4 ASJ exome

AF:

0.689

Gnomad4 EAS exome

AF:

0.720

Gnomad4 SAS exome

AF:

0.712

Gnomad4 FIN exome

AF:

0.613

Gnomad4 NFE exome

AF:

0.643

Gnomad4 OTH exome

AF:

0.670

GnomAD4 genome

AF:

0.683

AC:

103944

AN:

152222

Hom.:

35758

Cov.:

AF XY:

0.680

AC XY:

50603

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.752

Gnomad4 AMR

AF:

0.633

Gnomad4 ASJ

AF:

0.701

Gnomad4 EAS

AF:

0.747

Gnomad4 SAS

AF:

0.711

Gnomad4 FIN

AF:

0.607

Gnomad4 NFE

AF:

0.656

Gnomad4 OTH

AF:

0.705

Alfa

AF:

0.659

Hom.:

18444

Bravo

AF:

0.685

Asia WGS

AF:

0.716

AC:

2487

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 26, 2016	Variant summary: The SUFU c.1365+19T>C variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts the variant to be neutral along with 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 80437/121368 control chromosomes (including 26892 homozygotes) at a frequency of 0.6627529, indicating the variant to be the ancestral allele and a common benign polymorphism. Taken together, this variant is classified as Benign. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Joubert syndrome 32

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Gorlin syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Gorlin syndrome;C0025149:Medulloblastoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 04, 2025

- -

Familial meningioma

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.0

DANN

Benign

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over