rs3862030

Positions:

• chr10-102567827-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SUFU	NM_016169.4	c.454+17721A>G		intron_variant		ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8	c.454+17721A>G		intron_variant		1	NM_016169.4	ENSP00000358918	P1
SUFU	ENST00000369899.6	c.454+17721A>G		intron_variant		1		ENSP00000358915
SUFU	ENST00000423559.2	c.454+17721A>G		intron_variant		1		ENSP00000411597

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

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.441

Alfa AF: 0.435 Hom.: 1834

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

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

Other links and lift over

dbSNP: rs3862030; hg19: chr10-104327584;