rs10198539

Positions:

• chr2-230240931-C-T

Variant summary

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

The NM_007237.5(SP140):​c.407-473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,124 control chromosomes in the GnomAD database, including 1,505 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 0.13 (1505 hom., cov: 32)
• Consequence: SP140 NM_007237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP140	NM_007237.5	c.407-473C>T		intron_variant		ENST00000392045.8	NP_009168.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP140	ENST00000392045.8	c.407-473C>T		intron_variant		2	NM_007237.5	ENSP00000375899	A2
SP140	ENST00000343805.10	c.407-473C>T		intron_variant		1		ENSP00000342096	A2
SP140	ENST00000417495.7	c.407-473C>T		intron_variant		1		ENSP00000393618	P2
SP140	ENST00000420434.7	c.407-473C>T		intron_variant		1		ENSP00000398210	A2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20254 AN: 152006 Hom.: 1504 Cov.: 32

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.133 AC: 20252 AN: 152124 Hom.: 1505 Cov.: 32 AF XY: 0.128 AC XY: 9543 AN XY: 74356

Gnomad4 AFR AF: 0.0887

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.135

Alfa AF: 0.147 Hom.: 257

Bravo AF: 0.130

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.79

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: rs10198539; hg19: chr2-231105646;