2-230172639-T-G

Variant names:

• chr2-230172639-T-G
• rs2278198
• NM_080424.4:c.1706+205A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080424.4(SP110):​c.1706+205A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000463 in 432,110 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.689
• Publications: 0 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

ENSG00000225963 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.1706+205A>C		intron_variant	Intron 15 of 18	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.1706+205A>C		intron_variant	Intron 15 of 18	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000463 AC: 2 AN: 432110 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 228084

African (AFR) AF: 0.00 AC: 0 AN: 12184

American (AMR) AF: 0.00 AC: 0 AN: 19362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13232

East Asian (EAS) AF: 0.00 AC: 0 AN: 29518

South Asian (SAS) AF: 0.00 AC: 0 AN: 46062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1868

European-Non Finnish (NFE) AF: 0.00000777 AC: 2 AN: 257422

Other (OTH) AF: 0.00 AC: 0 AN: 24928

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.64
PhyloP100		0.69

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: rs2278198; hg19: chr2-231037355;