2-230245865-TC-AG

Variant names:

• chr2-230245865-TC-AG
• NM_007237.5:c.667_668delTCinsAG
• SP140 p.224

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The NM_007237.5(SP140):​c.667_668delTCinsAG​(p.224) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SP140 NM_007237.5 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 0 publications found

Genes affected

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: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=-0.113 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007237.5. 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
	SP140	NM_007237.5	MANE Select	c.667_668delTCinsAG	p.224	splice_region synonymous	N/A	NP_009168.4
	SP140	NM_001278451.2		c.667_668delTCinsAG	p.224	splice_region synonymous	N/A	NP_001265380.1	Q13342-5
	SP140	NM_001278453.2		c.658_659delTCinsAG	p.221	splice_region synonymous	N/A	NP_001265382.1	Q13342-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140	ENST00000392045.8	TSL:2 MANE Select	c.667_668delTCinsAG	p.224	splice_region synonymous	N/A	ENSP00000375899.3	Q13342-1
	SP140	ENST00000420434.7	TSL:1	c.667_668delTCinsAG	p.224	splice_region synonymous	N/A	ENSP00000398210.3	Q13342-5
	SP140	ENST00000417495.7	TSL:1	c.658_659delTCinsAG	p.221	splice_region synonymous	N/A	ENSP00000393618.3	Q13342-3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-231110580;