2-230230963-T-C

Position:

• chr2-230230963-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007237.5(SP140):​c.59+5060T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,236 control chromosomes in the GnomAD database, including 1,836 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 (1836 hom., cov: 32)
• Consequence: SP140 NM_007237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP140	NM_007237.5	c.59+5060T>C		intron_variant		ENST00000392045.8	NP_009168.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP140	ENST00000392045.8	c.59+5060T>C		intron_variant		2	NM_007237.5	ENSP00000375899	A2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22676 AN: 152118 Hom.: 1835 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.149 AC: 22673 AN: 152236 Hom.: 1836 Cov.: 32 AF XY: 0.145 AC XY: 10759 AN XY: 74450

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.149

Alfa AF: 0.163 Hom.: 306

Bravo AF: 0.145

Asia WGS AF: 0.0640 AC: 222 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.38
DANN	Benign	0.47

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: rs7563433; hg19: chr2-231095678;