2-230213153-A-G

Variant names:

• chr2-230213153-A-G
• rs7601176
• NM_080424.4:c.317-126T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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]

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	NM_080424.4	MANE Select	c.317-126T>C		intron	N/A	NP_536349.3
	SP110	NM_001378442.1		c.335-126T>C		intron	N/A	NP_001365371.1
	SP110	NM_001378443.1		c.317-126T>C		intron	N/A	NP_001365372.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.317-126T>C		intron	N/A	ENSP00000258381.6
	SP110	ENST00000358662.9	TSL:1	c.317-126T>C		intron	N/A	ENSP00000351488.4
	SP110	ENST00000258382.10	TSL:1	c.317-126T>C		intron	N/A	ENSP00000258382.5

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

African (AFR) AF: 0.818 AC: 16585 AN: 20272

American (AMR) AF: 0.662 AC: 24381 AN: 36852

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 13285 AN: 21154

East Asian (EAS) AF: 0.890 AC: 30827 AN: 34628

South Asian (SAS) AF: 0.760 AC: 52166 AN: 68660

European-Finnish (FIN) AF: 0.591 AC: 22000 AN: 37250

Middle Eastern (MID) AF: 0.623 AC: 1879 AN: 3014

European-Non Finnish (NFE) AF: 0.568 AC: 285379 AN: 502768

Other (OTH) AF: 0.623 AC: 23225 AN: 37302

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

African (AFR) AF: 0.823 AC: 34076 AN: 41428

American (AMR) AF: 0.647 AC: 9886 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2160 AN: 3470

East Asian (EAS) AF: 0.900 AC: 4641 AN: 5158

South Asian (SAS) AF: 0.781 AC: 3758 AN: 4814

European-Finnish (FIN) AF: 0.583 AC: 6142 AN: 10540

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38562 AN: 67968

Other (OTH) AF: 0.635 AC: 1341 AN: 2112

Alfa AF: 0.600 Hom.: 35966

Bravo AF: 0.675

Asia WGS AF: 0.844 AC: 2934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.049
DANN	Benign	0.75
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: rs7601176; hg19: chr2-231077868;