rs10201872

Variant names:

• chr2-230242009-C-T
• rs10201872
• NM_007237.5:c.490+522C>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.490+522C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,816 control chromosomes in the GnomAD database, including 1,509 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 (1509 hom., cov: 31)
• Consequence: SP140 NM_007237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 50 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=-0.9).
• 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 rank	MANE	Protein	UniProt
SP140	NM_007237.5	c.490+522C>T		intron_variant	Intron 4 of 26	ENST00000392045.8	NP_009168.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP140	ENST00000392045.8	c.490+522C>T		intron_variant	Intron 4 of 26	2	NM_007237.5	ENSP00000375899.3
SP140	ENST00000420434.7	c.490+522C>T		intron_variant	Intron 4 of 25	1		ENSP00000398210.3
SP140	ENST00000343805.10	c.490+522C>T		intron_variant	Intron 4 of 24	1		ENSP00000342096.6
SP140	ENST00000417495.7	c.490+522C>T		intron_variant	Intron 4 of 23	1		ENSP00000393618.3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20270 AN: 151698 Hom.: 1508 Cov.: 31

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.204

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: 0.134 AC: 20268 AN: 151816 Hom.: 1509 Cov.: 31 AF XY: 0.129 AC XY: 9552 AN XY: 74148

African (AFR) AF: 0.0894 AC: 3703 AN: 41406

American (AMR) AF: 0.122 AC: 1858 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3464

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5156

South Asian (SAS) AF: 0.139 AC: 667 AN: 4806

European-Finnish (FIN) AF: 0.103 AC: 1077 AN: 10498

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

European-Non Finnish (NFE) AF: 0.176 AC: 11931 AN: 67918

Other (OTH) AF: 0.136 AC: 287 AN: 2112

Alfa AF: 0.164 Hom.: 7097

Bravo AF: 0.131

Asia WGS AF: 0.0560 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.45
PhyloP100		-0.20
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: rs10201872; hg19: chr2-231106724;