rs7423615

Variant names:

• chr2-230252159-C-T
• rs7423615
• NM_007237.5:c.1057+1098C>T

Variant summary

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

The NM_007237.5(SP140):​c.1057+1098C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,088 control chromosomes in the GnomAD database, including 1,712 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 0.14 (1712 hom., cov: 30)
• Consequence: SP140 NM_007237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464
• Publications: 44 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

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.1057+1098C>T		intron	N/A	NP_009168.4
	SP140	NM_001278451.2		c.1057+1098C>T		intron	N/A	NP_001265380.1	Q13342-5
	SP140	NM_001278452.2		c.979+1098C>T		intron	N/A	NP_001265381.1	Q13342-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140	ENST00000392045.8	TSL:2 MANE Select	c.1057+1098C>T		intron	N/A	ENSP00000375899.3	Q13342-1
	SP140	ENST00000420434.7	TSL:1	c.1057+1098C>T		intron	N/A	ENSP00000398210.3	Q13342-5
	SP140	ENST00000343805.10	TSL:1	c.979+1098C>T		intron	N/A	ENSP00000342096.6	Q13342-6

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21515 AN: 150970 Hom.: 1711 Cov.: 30

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.000971

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.142 AC: 21511 AN: 151088 Hom.: 1712 Cov.: 30 AF XY: 0.138 AC XY: 10196 AN XY: 73722

African (AFR) AF: 0.0953 AC: 3914 AN: 41060

American (AMR) AF: 0.125 AC: 1901 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3470

East Asian (EAS) AF: 0.000973 AC: 5 AN: 5138

South Asian (SAS) AF: 0.158 AC: 750 AN: 4756

European-Finnish (FIN) AF: 0.125 AC: 1299 AN: 10368

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.185 AC: 12572 AN: 67834

Other (OTH) AF: 0.142 AC: 299 AN: 2102

Alfa AF: 0.156 Hom.: 2629

Bravo AF: 0.137

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.23
PhyloP100		-0.46
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: rs7423615; hg19: chr2-231116874;