rs4629211

chr2-138520934-G-Achr2-138520934-G-Cchr2-138520934-G-T

Variant summary

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

The NM_001001664.3(SPOPL):c.-61+18815G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,984 control chromosomes in the GnomAD database, including 1,885 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 (1885 hom., cov: 32)
• Consequence: SPOPL NM_001001664.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647

Genes affected

SPOPL (HGNC:27934): (speckle type BTB/POZ protein like) Predicted to enable ubiquitin protein ligase binding activity. Involved in negative regulation of protein ubiquitination and proteasome-mediated ubiquitin-dependent protein catabolic process. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

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 (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPOPL	NM_001001664.3	c.-61+18815G>A		intron_variant		ENST00000280098.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPOPL	ENST00000280098.9	c.-61+18815G>A		intron_variant		1	NM_001001664.3	P1
SPOPL	ENST00000430968.5	c.-61+18815G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22506 AN: 151866 Hom.: 1883 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.148 AC: 22527 AN: 151984 Hom.: 1885 Cov.: 32 AF XY: 0.147 AC XY: 10912 AN XY: 74316

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.163

Alfa AF: 0.131 Hom.: 414

Bravo AF: 0.149

Asia WGS AF: 0.0570 AC: 202 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.32
Dann	Benign	0.37

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: rs4629211; hg19: chr2-139278504;