rs10786691

chr10-102604895-G-Achr10-102604895-G-Cchr10-102604895-G-T

Variant summary

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

The NM_016169.4(SUFU):c.1022+5351G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 145,972 control chromosomes in the GnomAD database, including 15,434 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 (15434 hom., cov: 26)
• Consequence: SUFU NM_016169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUFU	NM_016169.4	c.1022+5351G>A		intron_variant		ENST00000369902.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUFU	ENST00000369902.8	c.1022+5351G>A		intron_variant		1	NM_016169.4	P1
SUFU	ENST00000369899.6	c.1022+5351G>A		intron_variant		1
SUFU	ENST00000423559.2	c.1022+5351G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 66575 AN: 145894 Hom.: 15408 Cov.: 26

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.456 AC: 66628 AN: 145972 Hom.: 15434 Cov.: 26 AF XY: 0.462 AC XY: 32583 AN XY: 70476

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.446

Alfa AF: 0.425 Hom.: 1719

Bravo AF: 0.465

Asia WGS AF: 0.598 AC: 2077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.0
Dann	Benign	0.34

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: rs10786691; hg19: chr10-104364652;