rs10514971

chr17-49661184-C-T

Variant summary

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

The NM_001007228.2(SPOP):c.-67+16749G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,084 control chromosomes in the GnomAD database, including 2,121 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 0.15 (2121 hom., cov: 31)
• Consequence: SPOP NM_001007228.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393

Genes affected

SPOP (HGNC:11254): (speckle type BTB/POZ protein) This gene encodes a protein that may modulate the transcriptional repression activities of death-associated protein 6 (DAXX), which interacts with histone deacetylase, core histones, and other histone-associated proteins. In mouse, the encoded protein binds to the putative leucine zipper domain of macroH2A1.2, a variant H2A histone that is enriched on inactivated X chromosomes. The BTB/POZ domain of this protein has been shown in other proteins to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes. Alternative splicing of this gene results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPOP	NM_001007228.2	c.-67+16749G>A		intron_variant		ENST00000504102.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPOP	ENST00000504102.6	c.-67+16749G>A		intron_variant		1	NM_001007228.2	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22275 AN: 151966 Hom.: 2119 Cov.: 31

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0659

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.146 AC: 22278 AN: 152084 Hom.: 2121 Cov.: 31 AF XY: 0.145 AC XY: 10783 AN XY: 74340

Gnomad4 AFR AF: 0.0388

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0662

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.146

Alfa AF: 0.195 Hom.: 2887

Bravo AF: 0.141

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.2
Dann	Benign	0.52

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: rs10514971; hg19: chr17-47738546;