rs12435998

chr14-81506329-T-C

Variant summary

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

The NM_005065.6(SEL1L):c.341-88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,196,468 control chromosomes in the GnomAD database, including 21,465 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 0.14 (1979 hom., cov: 32)
  • Exomes 𝑓: 0.19 (19486 hom.)
• Consequence: SEL1L NM_005065.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

Genes affected

SEL1L (HGNC:10717): (SEL1L adaptor subunit of SYVN1 ubiquitin ligase) The protein encoded by this gene is part of a protein complex required for the retrotranslocation or dislocation of misfolded proteins from the endoplasmic reticulum lumen to the cytosol, where they are degraded by the proteasome in a ubiquitin-dependent manner. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEL1L	NM_005065.6	c.341-88A>G		intron_variant		ENST00000336735.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEL1L	ENST00000336735.9	c.341-88A>G		intron_variant		1	NM_005065.6	P1
SEL1L	ENST00000555824.5	c.341-88A>G		intron_variant		1
SEL1L	ENST00000557372.1	c.341-151A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22065 AN: 152108 Hom.: 1981 Cov.: 32

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.191 AC: 199497 AN: 1044242 Hom.: 19486 AF XY: 0.191 AC XY: 98440 AN XY: 516402

Gnomad4 AFR exome AF: 0.0350

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.145 AC: 22067 AN: 152226 Hom.: 1979 Cov.: 32 AF XY: 0.143 AC XY: 10632 AN XY: 74420

Gnomad4 AFR AF: 0.0403

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.148

Alfa AF: 0.187 Hom.: 4815

Bravo AF: 0.140

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.033
Dann	Benign	0.65

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: rs12435998; hg19: chr14-81972673;