rs3862030

Variant names:

• chr10-102567827-A-G
• rs3862030
• NM_016169.4:c.454+17721A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016169.4(SUFU):​c.454+17721A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,784 control chromosomes in the GnomAD database, including 16,007 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16007 hom., cov: 30)
• Consequence: SUFU NM_016169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 11 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUFU	NM_016169.4	c.454+17721A>G		intron_variant	Intron 3 of 11	ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8	c.454+17721A>G		intron_variant	Intron 3 of 11	1	NM_016169.4	ENSP00000358918.4
SUFU	ENST00000423559.2	c.454+17721A>G		intron_variant	Intron 3 of 9	1		ENSP00000411597.2
SUFU	ENST00000369899.6	c.454+17721A>G		intron_variant	Intron 3 of 10	1		ENSP00000358915.2

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68784 AN: 151664 Hom.: 15979 Cov.: 30

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.454 AC: 68844 AN: 151784 Hom.: 16007 Cov.: 30 AF XY: 0.459 AC XY: 34067 AN XY: 74158

African (AFR) AF: 0.449 AC: 18593 AN: 41394

American (AMR) AF: 0.551 AC: 8389 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1100 AN: 3470

East Asian (EAS) AF: 0.674 AC: 3468 AN: 5144

South Asian (SAS) AF: 0.510 AC: 2454 AN: 4816

European-Finnish (FIN) AF: 0.444 AC: 4673 AN: 10516

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28656 AN: 67918

Other (OTH) AF: 0.441 AC: 929 AN: 2106

Alfa AF: 0.436 Hom.: 1916

Bravo AF: 0.465

Asia WGS AF: 0.598 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		-1.5
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: rs3862030; hg19: chr10-104327584;