rs11191325

Positions:

• chr10-102543176-G-A
• chr10-102543176-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.318-6794G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,900 control chromosomes in the GnomAD database, including 7,330 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 0.30 (7330 hom., cov: 32)
• Consequence: SUFU NM_016169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUFU	NM_016169.4	c.318-6794G>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.318-6794G>A		intron_variant		1	NM_016169.4	ENSP00000358918	P1
SUFU	ENST00000369899.6	c.318-6794G>A		intron_variant		1		ENSP00000358915
SUFU	ENST00000423559.2	c.318-6794G>A		intron_variant		1		ENSP00000411597

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46242 AN: 151784 Hom.: 7329 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.305 AC: 46256 AN: 151900 Hom.: 7330 Cov.: 32 AF XY: 0.308 AC XY: 22835 AN XY: 74222

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.282

Alfa AF: 0.323 Hom.: 3518

Bravo AF: 0.301

Asia WGS AF: 0.285 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.82

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: rs11191325; hg19: chr10-104302933;