rs34034766

Variant names:

• chr2-230172052-T-C
• rs34034766
• NM_080424.4:c.1815+14A>G

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -3.05
• Publications: 4 publications found

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]

SP110 Gene-Disease associations (from GenCC):

• hepatic veno-occlusive disease-immunodeficiency syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, ClinGen, Ambry Genetics

ENSG00000225963 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 334896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080424.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	NM_080424.4	MANE Select	c.1815+14A>G		intron	N/A	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.1833+14A>G		intron	N/A	NP_001365371.1
	SP110	NM_001378443.1		c.1815+14A>G		intron	N/A	NP_001365372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.1815+14A>G		intron	N/A	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.1815+14A>G		intron	N/A	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000897327.1		c.1815+14A>G		intron	N/A	ENSP00000567386.1

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

GnomAD2 exomes AF: 0.0975 AC: 24505 AN: 251248 AF XY: 0.0975

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 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

African (AFR) AF: 0.118 AC: 3639 AN: 30904

American (AMR) AF: 0.0812 AC: 3619 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.0978 AC: 2472 AN: 25274

East Asian (EAS) AF: 0.000511 AC: 20 AN: 39110

South Asian (SAS) AF: 0.0727 AC: 6084 AN: 83724

European-Finnish (FIN) AF: 0.0913 AC: 4860 AN: 53258

Middle Eastern (MID) AF: 0.116 AC: 641 AN: 5532

European-Non Finnish (NFE) AF: 0.122 AC: 120546 AN: 987940

Other (OTH) AF: 0.108 AC: 6055 AN: 55980

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

African (AFR) AF: 0.117 AC: 4867 AN: 41562

American (AMR) AF: 0.104 AC: 1597 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3472

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5186

South Asian (SAS) AF: 0.0626 AC: 302 AN: 4828

European-Finnish (FIN) AF: 0.0858 AC: 910 AN: 10610

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8264 AN: 68028

Other (OTH) AF: 0.108 AC: 228 AN: 2116

Alfa AF: 0.113 Hom.: 184

Bravo AF: 0.112

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hepatic veno-occlusive disease-immunodeficiency syndrome (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.026
DANN	Benign	0.32
PhyloP100		-3.1
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: rs34034766; hg19: chr2-231036768;