rs7078511

Positions:

• chr10-102524117-C-A
• chr10-102524117-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016169.4(SUFU):​c.317+14814C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,738 control chromosomes in the GnomAD database, including 17,165 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 0.46 (17165 hom., cov: 30)
• Consequence: SUFU NM_016169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401

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 (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUFU	NM_016169.4	c.317+14814C>A		intron_variant		ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8	c.317+14814C>A		intron_variant		1	NM_016169.4	ENSP00000358918	P1
SUFU	ENST00000369899.6	c.317+14814C>A		intron_variant		1		ENSP00000358915
SUFU	ENST00000423559.2	c.317+14814C>A		intron_variant		1		ENSP00000411597

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70074 AN: 151620 Hom.: 17161 Cov.: 30

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.462 AC: 70096 AN: 151738 Hom.: 17165 Cov.: 30 AF XY: 0.458 AC XY: 33980 AN XY: 74160

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.499

Alfa AF: 0.365 Hom.: 1157

Bravo AF: 0.443

Asia WGS AF: 0.385 AC: 1340 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	1.8
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: rs7078511; hg19: chr10-104283874;