2-230181227-G-C

Variant names:

• chr2-230181227-G-C
• rs4973285
• NM_080424.4:c.1348+2345C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080424.4(SP110):​c.1348+2345C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,174 control chromosomes in the GnomAD database, including 47,908 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 0.79 (47908 hom., cov: 32)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 2 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), Orphanet, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.1348+2345C>G		intron_variant	Intron 12 of 18	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.1348+2345C>G		intron_variant	Intron 12 of 18	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120536 AN: 152056 Hom.: 47870 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.784

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

GnomAD4 genome AF: 0.793 AC: 120629 AN: 152174 Hom.: 47908 Cov.: 32 AF XY: 0.793 AC XY: 58970 AN XY: 74376

African (AFR) AF: 0.823 AC: 34162 AN: 41510

American (AMR) AF: 0.837 AC: 12808 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2575 AN: 3470

East Asian (EAS) AF: 0.814 AC: 4206 AN: 5170

South Asian (SAS) AF: 0.677 AC: 3266 AN: 4824

European-Finnish (FIN) AF: 0.802 AC: 8481 AN: 10572

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52533 AN: 68008

Other (OTH) AF: 0.784 AC: 1657 AN: 2114

Alfa AF: 0.697 Hom.: 2004

Bravo AF: 0.800

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.65
PhyloP100		-1.2
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: rs4973285; hg19: chr2-231045943;