dbSNP rs6142963: SS18L1:c.70-89A>G (chr20-62158583-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198935.3(SS18L1):c.70-89A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 1,542,584 control chromosomes in the GnomAD database, including 4,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 491 hom., cov: 32)

Exomes 𝑓: 0.068 ( 4249 hom. )

Consequence

SS18L1
NM_198935.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.76

Publications

5 publications found

Variant links:

Genes affected

SS18L1 (HGNC:15592): (SS18L1 subunit of BAF chromatin remodeling complex) This gene encodes a calcium-responsive transactivator which is an essential subunit of a neuron-specific chromatin-remodeling complex. The structure of this gene is similar to that of the SS18 gene. Mutations in this gene are involved in amyotrophic lateral sclerosis (ALS). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

SS18L1 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Genomics England PanelApp, ClinGen

SS18L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 20-62158583-A-G is Benign according to our data. Variant chr20-62158583-A-G is described in ClinVar as [Benign]. Clinvar id is 1182966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SS18L1	NM_198935.3 link	c.70-89A>G		intron_variant	Intron 1 of 10	ENST00000331758.8	NP_945173.1	O75177-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SS18L1	ENST00000331758.8 link	c.70-89A>G		intron_variant	Intron 1 of 10	1	NM_198935.3	ENSP00000333012.3		O75177-1
SS18L1	ENST00000450482.5 link	c.-116-89A>G		intron_variant	Intron 2 of 4	5		ENSP00000398634.1		Q9BR54

Frequencies

GnomAD3 genomes

AF:

0.0716

AC:

10894

AN:

152166

Hom.:

490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0752

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0535

Gnomad ASJ

AF:

0.0786

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.0741

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0578

Gnomad OTH

AF:

0.0516

GnomAD4 exome

AF:

0.0680

AC:

94471

AN:

1390300

Hom.:

4249

AF XY:

0.0716

AC XY:

49156

AN XY:

686712

show subpopulations

African (AFR)

AF:

0.0753

AC:

2397

AN:

31848

American (AMR)

AF:

0.0489

AC:

1787

AN:

36546

Ashkenazi Jewish (ASJ)

AF:

0.0849

AC:

2132

AN:

25120

East Asian (EAS)

AF:

0.136

AC:

5006

AN:

36716

South Asian (SAS)

AF:

0.178

AC:

14498

AN:

81332

European-Finnish (FIN)

AF:

0.0674

AC:

2632

AN:

39042

Middle Eastern (MID)

AF:

0.0495

AC:

220

AN:

4440

European-Non Finnish (NFE)

AF:

0.0572

AC:

61660

AN:

1077284

Other (OTH)

AF:

0.0714

AC:

4139

AN:

57972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

4591

9182

13774

18365

22956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0716

AC:

10908

AN:

152284

Hom.:

491

Cov.:

AF XY:

0.0751

AC XY:

5591

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0753

AC:

3129

AN:

41560

American (AMR)

AF:

0.0534

AC:

817

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0786

AC:

273

AN:

3472

East Asian (EAS)

AF:

0.173

AC:

895

AN:

5178

South Asian (SAS)

AF:

0.193

AC:

933

AN:

4824

European-Finnish (FIN)

AF:

0.0741

AC:

786

AN:

10606

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0578

AC:

3930

AN:

68022

Other (OTH)

AF:

0.0543

AC:

115

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

538

1076

1614

2152

2690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0615

Hom.:

580

Bravo

AF:

0.0674

Asia WGS

AF:

0.173

AC:

600

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 16, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.066

(source)

DANN

Benign

0.069

PhyloP100

-1.8

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

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rs6142963

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over