chr2-230226508-T-G

Variant names:

• chr2-230226508-T-G
• rs13397985
• NM_007237.5:c.59+605T>G

Variant summary

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

The NM_007237.5(SP140):​c.59+605T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,148 control chromosomes in the GnomAD database, including 1,803 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 0.15 (1803 hom., cov: 31)
• Consequence: SP140 NM_007237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 66 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140	NM_007237.5	MANE Select	c.59+605T>G		intron	N/A	NP_009168.4
	SP140	NM_001278451.2		c.59+605T>G		intron	N/A	NP_001265380.1
	SP140	NM_001278452.2		c.59+605T>G		intron	N/A	NP_001265381.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140	ENST00000392045.8	TSL:2 MANE Select	c.59+605T>G		intron	N/A	ENSP00000375899.3
	SP140	ENST00000420434.7	TSL:1	c.59+605T>G		intron	N/A	ENSP00000398210.3
	SP140	ENST00000343805.10	TSL:1	c.59+605T>G		intron	N/A	ENSP00000342096.6

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22336 AN: 152030 Hom.: 1802 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.147 AC: 22332 AN: 152148 Hom.: 1803 Cov.: 31 AF XY: 0.142 AC XY: 10582 AN XY: 74402

African (AFR) AF: 0.108 AC: 4489 AN: 41518

American (AMR) AF: 0.127 AC: 1944 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3470

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5192

South Asian (SAS) AF: 0.162 AC: 780 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1302 AN: 10584

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12719 AN: 67972

Other (OTH) AF: 0.148 AC: 312 AN: 2112

Alfa AF: 0.172 Hom.: 10185

Bravo AF: 0.142

Asia WGS AF: 0.0640 AC: 224 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.69
PhyloP100		1.9
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: rs13397985; hg19: chr2-231091223;