2-230480845-C-A

Variant names:

• chr2-230480845-C-A
• rs1678199
• NM_001080391.2:c.1600+6398C>A

Variant summary

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

The NM_001080391.2(SP100):​c.1600+6398C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,182 control chromosomes in the GnomAD database, including 58,065 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 0.87 (58065 hom., cov: 31)
• Consequence: SP100 NM_001080391.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• Publications: 1 publications found

Genes affected

SP100 (HGNC:11206): (SP100 nuclear antigen) This gene encodes a subnuclear organelle and major component of the PML (promyelocytic leukemia)-SP100 nuclear bodies. PML and SP100 are covalently modified by the SUMO-1 modifier, which is considered crucial to nuclear body interactions. The encoded protein binds heterochromatin proteins and is thought to play a role in tumorigenesis, immunity, and gene regulation. Alternatively spliced variants have been identified for this gene; one of which encodes a high-mobility group protein. [provided by RefSeq, Aug 2011]

ENSG00000308860 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080391.2. 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
	SP100	NM_001080391.2	MANE Select	c.1600+6398C>A		intron	N/A	NP_001073860.1	P23497-4
	SP100	NM_003113.4		c.1600+6398C>A		intron	N/A	NP_003104.2
	SP100	NM_001206701.2		c.1600+6398C>A		intron	N/A	NP_001193630.1	P23497-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP100	ENST00000340126.9	TSL:1 MANE Select	c.1600+6398C>A		intron	N/A	ENSP00000343023.4	P23497-4
	SP100	ENST00000264052.9	TSL:1	c.1600+6398C>A		intron	N/A	ENSP00000264052.5	P23497-1
	SP100	ENST00000409112.5	TSL:1	c.1600+6398C>A		intron	N/A	ENSP00000386427.1	P23497-3

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132115 AN: 152064 Hom.: 58010 Cov.: 31

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.869 AC: 132221 AN: 152182 Hom.: 58065 Cov.: 31 AF XY: 0.864 AC XY: 64297 AN XY: 74396

African (AFR) AF: 0.966 AC: 40138 AN: 41552

American (AMR) AF: 0.760 AC: 11628 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3215 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3027 AN: 5170

South Asian (SAS) AF: 0.878 AC: 4228 AN: 4814

European-Finnish (FIN) AF: 0.853 AC: 9019 AN: 10572

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58138 AN: 67996

Other (OTH) AF: 0.874 AC: 1844 AN: 2110

Alfa AF: 0.919 Hom.: 10136

Bravo AF: 0.862

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.91
DANN	Benign	0.65
PhyloP100		-0.40
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: rs1678199; hg19: chr2-231345560;