chr17-49616324-G-T

Variant names:

• chr17-49616324-G-T
• rs2676801
• NM_001007228.2:c.480+2657C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

SPOP Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with microcephaly and dysmorphic facies

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies

  Inheritance: AD Classification: STRONG Submitted by: G2P

LOC107984999 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007228.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOP	NM_001007228.2	MANE Select	c.480+2657C>A		intron	N/A	NP_001007229.1
	SPOP	NM_001007226.1		c.480+2657C>A		intron	N/A	NP_001007227.1
	SPOP	NM_001007227.1		c.480+2657C>A		intron	N/A	NP_001007228.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOP	ENST00000504102.6	TSL:1 MANE Select	c.480+2657C>A		intron	N/A	ENSP00000425905.1
	SPOP	ENST00000393328.6	TSL:1	c.480+2657C>A		intron	N/A	ENSP00000377001.2
	SPOP	ENST00000347630.6	TSL:5	c.480+2657C>A		intron	N/A	ENSP00000240327.2

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

African (AFR) AF: 0.0543 AC: 2254 AN: 41520

American (AMR) AF: 0.0471 AC: 720 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1083 AN: 5168

South Asian (SAS) AF: 0.0918 AC: 442 AN: 4816

European-Finnish (FIN) AF: 0.0564 AC: 597 AN: 10576

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0800 AC: 5440 AN: 67988

Other (OTH) AF: 0.0691 AC: 146 AN: 2114

Alfa AF: 0.0765 Hom.: 824

Bravo AF: 0.0701

Asia WGS AF: 0.128 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.39
DANN	Benign	0.68
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2676801; hg19: chr17-47693686;