rs10748825

chr10-102533852-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.318-16118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,088 control chromosomes in the GnomAD database, including 9,401 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 0.35 (9401 hom., cov: 32)
• Consequence: SUFU NM_016169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUFU	NM_016169.4	c.318-16118A>G		intron_variant		ENST00000369902.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUFU	ENST00000369902.8	c.318-16118A>G		intron_variant		1	NM_016169.4	P1
SUFU	ENST00000369899.6	c.318-16118A>G		intron_variant		1
SUFU	ENST00000423559.2	c.318-16118A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52959 AN: 151968 Hom.: 9390 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.348 AC: 52991 AN: 152088 Hom.: 9401 Cov.: 32 AF XY: 0.350 AC XY: 26003 AN XY: 74352

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.310

Alfa AF: 0.343 Hom.: 1493

Bravo AF: 0.352

Asia WGS AF: 0.294 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.6
Dann	Benign	0.67

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: rs10748825; hg19: chr10-104293609;