dbSNP rs12435998: SEL1L:c.341-88A>G (chr14-81506329-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.93

Publications

12 publications found

Variant links:

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]

SEL1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SEL1L	NM_005065.6 link	c.341-88A>G		intron_variant	Intron 3 of 20	ENST00000336735.9	NP_005056.3	Q9UBV2-1Q3ZCU6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEL1L	ENST00000336735.9 link	c.341-88A>G	intron_variant	Intron 3 of 20	1	NM_005065.6	ENSP00000337053.4	Q9UBV2-1
SEL1L	ENST00000555824.5 link	c.341-88A>G	intron_variant	Intron 3 of 7	1		ENSP00000450709.1	Q9UBV2-2
SEL1L	ENST00000557372.1 link	c.341-151A>G	intron_variant	Intron 3 of 4	3		ENSP00000451144.1	G3V3B3
SEL1L	ENST00000554744.1 link	n.-174A>G	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22065

AN:

152108

Hom.:

1981

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0350

AC:

771

AN:

22000

American (AMR)

AF:

0.143

AC:

2559

AN:

17842

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

3339

AN:

17000

East Asian (EAS)

AF:

0.206

AC:

6468

AN:

31436

South Asian (SAS)

AF:

0.148

AC:

7974

AN:

53908

European-Finnish (FIN)

AF:

0.190

AC:

7559

AN:

39886

Middle Eastern (MID)

AF:

0.178

AC:

556

AN:

3130

European-Non Finnish (NFE)

AF:

0.199

AC:

162344

AN:

814128

Other (OTH)

AF:

0.177

AC:

7927

AN:

44912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

7637

15274

22912

30549

38186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5636

11272

16908

22544

28180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.145

AC:

22067

AN:

152226

Hom.:

1979

Cov.:

AF XY:

0.143

AC XY:

10632

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0403

AC:

1676

AN:

41568

American (AMR)

AF:

0.147

AC:

2248

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

727

AN:

3472

East Asian (EAS)

AF:

0.185

AC:

957

AN:

5166

South Asian (SAS)

AF:

0.135

AC:

652

AN:

4828

European-Finnish (FIN)

AF:

0.181

AC:

1922

AN:

10598

Middle Eastern (MID)

AF:

0.185

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.193

AC:

13135

AN:

67994

Other (OTH)

AF:

0.148

AC:

312

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

965

1931

2896

3862

4827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.175

Hom.:

7521

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

(source)

DANN

Benign

0.65

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over