rs7963934

Positions:

• chr12-48083303-C-G

Variant summary

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

The NM_001267594.2(SENP1):​c.552+288G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,072 control chromosomes in the GnomAD database, including 4,586 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 0.23 (4586 hom., cov: 32)
• Consequence: SENP1 NM_001267594.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SENP1	NM_001267594.2	c.552+288G>C		intron_variant		ENST00000549518.6	NP_001254523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SENP1	ENST00000549518.6	c.552+288G>C		intron_variant		1	NM_001267594.2	ENSP00000447328.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34503 AN: 151954 Hom.: 4574 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.227 AC: 34544 AN: 152072 Hom.: 4586 Cov.: 32 AF XY: 0.236 AC XY: 17561 AN XY: 74322

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.227

Alfa AF: 0.204 Hom.: 420

Bravo AF: 0.239

Asia WGS AF: 0.434 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.95
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: rs7963934; hg19: chr12-48477086;