2-230245867-C-T

Variant names:

• chr2-230245867-C-T
• rs28445040
• NM_007237.5:c.669C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007237.5(SP140):​c.669C>T​(p.Ser223Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,594,098 control chromosomes in the GnomAD database, including 24,594 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 (1844 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22750 hom.)
• Consequence: SP140 NM_007237.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 36 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.109 with no splicing effect.
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140	NM_007237.5	MANE Select	c.669C>T	p.Ser223Ser	synonymous	Exon 7 of 27	NP_009168.4
	SP140	NM_001278451.2		c.669C>T	p.Ser223Ser	synonymous	Exon 7 of 26	NP_001265380.1	Q13342-5
	SP140	NM_001278453.2		c.660C>T	p.Ser220Ser	synonymous	Exon 7 of 24	NP_001265382.1	Q13342-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140	ENST00000392045.8	TSL:2 MANE Select	c.669C>T	p.Ser223Ser	synonymous	Exon 7 of 27	ENSP00000375899.3	Q13342-1
	SP140	ENST00000420434.7	TSL:1	c.669C>T	p.Ser223Ser	synonymous	Exon 7 of 26	ENSP00000398210.3	Q13342-5
	SP140	ENST00000417495.7	TSL:1	c.660C>T	p.Ser220Ser	synonymous	Exon 7 of 24	ENSP00000393618.3	Q13342-3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22740 AN: 152100 Hom.: 1842 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.151

GnomAD2 exomes AF: 0.149 AC: 37104 AN: 248796 AF XY: 0.155

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.00251

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.172 AC: 247608 AN: 1441880 Hom.: 22750 Cov.: 28 AF XY: 0.173 AC XY: 124182 AN XY: 718368

African (AFR) AF: 0.117 AC: 3871 AN: 33164

American (AMR) AF: 0.110 AC: 4915 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 4746 AN: 26000

East Asian (EAS) AF: 0.00129 AC: 51 AN: 39656

South Asian (SAS) AF: 0.170 AC: 14600 AN: 85878

European-Finnish (FIN) AF: 0.126 AC: 6709 AN: 53354

Middle Eastern (MID) AF: 0.217 AC: 1241 AN: 5730

European-Non Finnish (NFE) AF: 0.184 AC: 201675 AN: 1093754

Other (OTH) AF: 0.164 AC: 9800 AN: 59722

GnomAD4 genome AF: 0.149 AC: 22745 AN: 152218 Hom.: 1844 Cov.: 32 AF XY: 0.145 AC XY: 10781 AN XY: 74432

African (AFR) AF: 0.119 AC: 4932 AN: 41520

American (AMR) AF: 0.129 AC: 1967 AN: 15300

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

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.157 AC: 758 AN: 4826

European-Finnish (FIN) AF: 0.124 AC: 1310 AN: 10606

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12678 AN: 68000

Other (OTH) AF: 0.150 AC: 316 AN: 2112

Alfa AF: 0.177 Hom.: 3899

Bravo AF: 0.145

Asia WGS AF: 0.0640 AC: 225 AN: 3478

EpiCase AF: 0.188

EpiControl AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.30
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs28445040; hg19: chr2-231110582;