rs34034766

Positions:

• chr2-230172052-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080424.4(SP110):​c.1815+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,478,622 control chromosomes in the GnomAD database, including 9,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (981 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9003 hom.)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.05

Genes affected

SP110 (HGNC:5401): (SP110 nuclear body protein) The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-230172052-T-C is Benign according to our data. Variant chr2-230172052-T-C is described in ClinVar as [Benign]. Clinvar id is 334896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-230172052-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP110	NM_080424.4	c.1815+14A>G		intron_variant		ENST00000258381.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP110	ENST00000258381.11	c.1815+14A>G		intron_variant		2	NM_080424.4	P1
	ENST00000628587.2	n.1004-47T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16647 AN: 152200 Hom.: 980 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.108

GnomAD3 exomes AF: 0.0975 AC: 24505 AN: 251248 Hom.: 1406 AF XY: 0.0975 AC XY: 13235 AN XY: 135784

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.0798

Gnomad ASJ exome AF: 0.0984

Gnomad EAS exome AF: 0.000816

Gnomad SAS exome AF: 0.0719

Gnomad FIN exome AF: 0.0874

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.0998

GnomAD4 exome AF: 0.112 AC: 147936 AN: 1326304 Hom.: 9003 Cov.: 20 AF XY: 0.111 AC XY: 73825 AN XY: 667134

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.0812

Gnomad4 ASJ exome AF: 0.0978

Gnomad4 EAS exome AF: 0.000511

Gnomad4 SAS exome AF: 0.0727

Gnomad4 FIN exome AF: 0.0913

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.109 AC: 16668 AN: 152318 Hom.: 981 Cov.: 33 AF XY: 0.107 AC XY: 7983 AN XY: 74480

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0626

Gnomad4 FIN AF: 0.0858

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.108

Alfa AF: 0.113 Hom.: 184

Bravo AF: 0.112

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.026
DANN	Benign	0.32

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: rs34034766; hg19: chr2-231036768;