rs2676801

Positions:

• chr17-49616324-G-T

Variant summary

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

The NM_001007228.2(SPOP):​c.480+2657C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0716 in 152,136 control chromosomes in the GnomAD database, including 491 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 0.072 (491 hom., cov: 32)
• Consequence: SPOP NM_001007228.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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]

LOC107984999 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOP	NM_001007228.2	c.480+2657C>A		intron_variant		ENST00000504102.6	NP_001007229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPOP	ENST00000504102.6	c.480+2657C>A		intron_variant		1	NM_001007228.2	ENSP00000425905.1

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10894 AN: 152018 Hom.: 490 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.0564

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.0698

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

GnomAD4 genome AF: 0.0716 AC: 10889 AN: 152136 Hom.: 491 Cov.: 32 AF XY: 0.0715 AC XY: 5321 AN XY: 74378

Gnomad4 AFR AF: 0.0543

Gnomad4 AMR AF: 0.0471

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.0918

Gnomad4 FIN AF: 0.0564

Gnomad4 NFE AF: 0.0800

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0777 Hom.: 674

Bravo AF: 0.0701

Asia WGS AF: 0.128 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.39
DANN	Benign	0.68

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: rs2676801; hg19: chr17-47693686;