12-48090833-G-C

Position:

• chr12-48090833-G-C

Variant summary

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

The NM_001267594.2(SENP1):​c.221-1873C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,100 control chromosomes in the GnomAD database, including 1,473 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 0.12 (1473 hom., cov: 32)
• Consequence: SENP1 NM_001267594.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555

Genes affected

SENP1 (HGNC:17927): (SUMO specific peptidase 1) This gene encodes a cysteine protease that specifically targets members of the small ubiquitin-like modifier (SUMO) protein family. This protease regulates SUMO pathways by deconjugating sumoylated proteins. This protease also functions to process the precursor SUMO proteins into their mature form. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SENP1	NM_001267594.2	c.221-1873C>G		intron_variant		ENST00000549518.6	NP_001254523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SENP1	ENST00000549518.6	c.221-1873C>G		intron_variant		1	NM_001267594.2	ENSP00000447328	P4

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18493 AN: 151982 Hom.: 1462 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0698

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.122 AC: 18540 AN: 152100 Hom.: 1473 Cov.: 32 AF XY: 0.119 AC XY: 8865 AN XY: 74374

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0980

Gnomad4 OTH AF: 0.100

Alfa AF: 0.112 Hom.: 144

Bravo AF: 0.122

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.48

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: rs12301562; hg19: chr12-48484616;