rs17226852

chr20-13993114-T-C

Variant summary

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

The ENST00000486903.5(SEL1L2):c.-279+1909A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0676 in 152,198 control chromosomes in the GnomAD database, including 397 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 0.068 (397 hom., cov: 32)
• Consequence: SEL1L2 ENST00000486903.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

Genes affected

SEL1L2 (HGNC:15897): (SEL1L2 adaptor subunit of SYVN1 ubiquitin ligase) Predicted to contribute to ubiquitin-protein transferase activity. Predicted to be involved in ubiquitin-dependent ERAD pathway. Predicted to be integral component of membrane. Predicted to be part of Hrd1p ubiquitin ligase ERAD-L complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEL1L2	NM_001363752.2	c.-279+1909A>G		intron_variant
SEL1L2	XM_047440521.1	c.-279+1909A>G		intron_variant
SEL1L2	NR_073207.2	n.311+1909A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEL1L2	ENST00000486903.5	c.-279+1909A>G		intron_variant, NMD_transcript_variant		1
SEL1L2	ENST00000473203.1	c.-279+3206A>G		intron_variant		4
SEL1L2	ENST00000646153.1	c.-279+1909A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0676 AC: 10283 AN: 152080 Hom.: 395 Cov.: 32

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.0828

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0785

Gnomad OTH AF: 0.0795

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

GnomAD4 genome AF: 0.0676 AC: 10294 AN: 152198 Hom.: 397 Cov.: 32 AF XY: 0.0648 AC XY: 4822 AN XY: 74406

Gnomad4 AFR AF: 0.0694

Gnomad4 AMR AF: 0.0582

Gnomad4 ASJ AF: 0.0828

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0506

Gnomad4 FIN AF: 0.0339

Gnomad4 NFE AF: 0.0785

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0753 Hom.: 565

Bravo AF: 0.0704

Asia WGS AF: 0.0230 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	9.4
Dann	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17226852; hg19: chr20-13973760;