2-230252159-C-T

Position:

• chr2-230252159-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.1057+1098C>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 151,088 control chromosomes in the GnomAD database, including 1,712 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 (1712 hom., cov: 30)
• Consequence: SP140 NM_007237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464

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=-0.97).
• 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/exons	MANE	Protein	UniProt
SP140	NM_007237.5	c.1057+1098C>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.1057+1098C>T		intron_variant		2	NM_007237.5	ENSP00000375899	A2
SP140	ENST00000343805.10	c.979+1098C>T		intron_variant		1		ENSP00000342096	A2
SP140	ENST00000417495.7	c.817+3191C>T		intron_variant		1		ENSP00000393618	P2
SP140	ENST00000420434.7	c.1057+1098C>T		intron_variant		1		ENSP00000398210	A2

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21515 AN: 150970 Hom.: 1711 Cov.: 30

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.000971

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.142 AC: 21511 AN: 151088 Hom.: 1712 Cov.: 30 AF XY: 0.138 AC XY: 10196 AN XY: 73722

Gnomad4 AFR AF: 0.0953

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.000973

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.142

Alfa AF: 0.161 Hom.: 1414

Bravo AF: 0.137

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.23

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: rs7423615; hg19: chr2-231116874;