rs4629211

Variant names:

• chr2-138520934-G-A
• rs4629211
• NM_001001664.3:c.-61+18815G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-138520934-G-A
• chr2-138520934-G-C
• chr2-138520934-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPOPL	NM_001001664.3	c.-61+18815G>A		intron_variant	Intron 1 of 10	ENST00000280098.9	NP_001001664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOPL	ENST00000280098.9	c.-61+18815G>A		intron_variant	Intron 1 of 10	1	NM_001001664.3	ENSP00000280098.4
SPOPL	ENST00000430968.5	n.-61+18815G>A		intron_variant	Intron 1 of 4	5		ENSP00000410201.1
SPOPL	ENST00000449869.2	n.-61+18815G>A		intron_variant	Intron 1 of 11	3		ENSP00000520629.1

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

African (AFR) AF: 0.222 AC: 9211 AN: 41444

American (AMR) AF: 0.123 AC: 1874 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5184

South Asian (SAS) AF: 0.103 AC: 497 AN: 4818

European-Finnish (FIN) AF: 0.156 AC: 1645 AN: 10540

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8282 AN: 67948

Other (OTH) AF: 0.163 AC: 342 AN: 2104

Alfa AF: 0.134 Hom.: 444

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
PhyloP100		-0.65
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: rs4629211; hg19: chr2-139278504;