rs7601176

chr2-230213153-A-Gchr2-230213153-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080424.4(SP110):c.317-126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 913,874 control chromosomes in the GnomAD database, including 183,195 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 0.67 (34867 hom., cov: 31)
  • Exomes 𝑓: 0.62 (148328 hom.)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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]

SP140 (HGNC:17133): (SP140 nuclear body protein) This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP110	NM_080424.4	c.317-126T>C		intron_variant		ENST00000258381.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP110	ENST00000258381.11	c.317-126T>C		intron_variant		2	NM_080424.4	P1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101122 AN: 151856 Hom.: 34829 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.632

GnomAD4 exome AF: 0.617 AC: 469727 AN: 761900 Hom.: 148328 AF XY: 0.622 AC XY: 247332 AN XY: 397750

Gnomad4 AFR exome AF: 0.818

Gnomad4 AMR exome AF: 0.662

Gnomad4 ASJ exome AF: 0.628

Gnomad4 EAS exome AF: 0.890

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.591

Gnomad4 NFE exome AF: 0.568

Gnomad4 OTH exome AF: 0.623

GnomAD4 genome AF: 0.666 AC: 101221 AN: 151974 Hom.: 34867 Cov.: 31 AF XY: 0.668 AC XY: 49632 AN XY: 74270

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.635

Alfa AF: 0.590 Hom.: 26515

Bravo AF: 0.675

Asia WGS AF: 0.844 AC: 2934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.049
Dann	Benign	0.75

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: rs7601176; hg19: chr2-231077868;