rs13385151

Variant names:

• chr2-230251261-C-T
• rs13385151
• NM_007237.5:c.1057+200C>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+200C>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 152,140 control chromosomes in the GnomAD database, including 1,718 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 (1718 hom., cov: 32)
• Consequence: SP140 NM_007237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP140	NM_007237.5	c.1057+200C>T		intron_variant	Intron 10 of 26	ENST00000392045.8	NP_009168.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP140	ENST00000392045.8	c.1057+200C>T		intron_variant	Intron 10 of 26	2	NM_007237.5	ENSP00000375899.3
SP140	ENST00000420434.7	c.1057+200C>T		intron_variant	Intron 10 of 25	1		ENSP00000398210.3
SP140	ENST00000343805.10	c.979+200C>T		intron_variant	Intron 9 of 24	1		ENSP00000342096.6
SP140	ENST00000417495.7	c.817+2293C>T		intron_variant	Intron 8 of 23	1		ENSP00000393618.3

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21610 AN: 152022 Hom.: 1717 Cov.: 32

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.142 AC: 21607 AN: 152140 Hom.: 1718 Cov.: 32 AF XY: 0.138 AC XY: 10243 AN XY: 74374

African (AFR) AF: 0.0953 AC: 3954 AN: 41504

American (AMR) AF: 0.125 AC: 1908 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3468

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.157 AC: 758 AN: 4828

European-Finnish (FIN) AF: 0.124 AC: 1308 AN: 10558

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12601 AN: 68012

Other (OTH) AF: 0.143 AC: 302 AN: 2108

Alfa AF: 0.156 Hom.: 290

Bravo AF: 0.137

Asia WGS AF: 0.0630 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.44
DANN	Benign	0.62
PhyloP100		-1.0
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: rs13385151; hg19: chr2-231115976;