rs989144

chr12-48090190-T-C

Variant summary

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

The NM_001267594.2(SENP1):c.221-1230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,248 control chromosomes in the GnomAD database, including 2,442 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 0.17 (2442 hom., cov: 32)
• Consequence: SENP1 NM_001267594.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SENP1	NM_001267594.2	c.221-1230A>G		intron_variant		ENST00000549518.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SENP1	ENST00000549518.6	c.221-1230A>G		intron_variant		1	NM_001267594.2	P4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25346 AN: 152130 Hom.: 2441 Cov.: 32

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.166 AC: 25346 AN: 152248 Hom.: 2442 Cov.: 32 AF XY: 0.164 AC XY: 12186 AN XY: 74442

Gnomad4 AFR AF: 0.0747

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.203

Alfa AF: 0.208 Hom.: 3945

Bravo AF: 0.166

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.092
Dann	Benign	0.67

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: rs989144; hg19: chr12-48483973;