Genetic Variant SS18L1:c.70-56C>T (chr20-62158616-C-T) – 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.70-56C>T 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 1,593,342 control chromosomes in the GnomAD database, including 4,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 480 hom., cov: 32)

Exomes 𝑓: 0.068 ( 4381 hom. )

Consequence

SS18L1
NM_198935.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.942

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:

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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=-0.87).

BP6

Variant 20-62158616-C-T is Benign according to our data. Variant chr20-62158616-C-T is described in ClinVar as [Benign]. Clinvar id is 1275993.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.70-56C>T		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.70-56C>T		intron_variant	Intron 1 of 10	1	NM_198935.3	ENSP00000333012.3		O75177-1
SS18L1	ENST00000450482.5 link	c.-116-56C>T		intron_variant	Intron 2 of 4	5		ENSP00000398634.1		Q9BR54

Frequencies

GnomAD3 genomes

AF:

0.0709

AC:

10790

AN:

152200

Hom.:

479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0727

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0534

Gnomad ASJ

AF:

0.0787

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:

0.0511

GnomAD4 exome

AF:

0.0680

AC:

97968

AN:

1441024

Hom.:

4381

AF XY:

0.0716

AC XY:

51210

AN XY:

715586

show subpopulations

African (AFR)

AF:

0.0716

AC:

2375

AN:

33162

American (AMR)

AF:

0.0488

AC:

2038

AN:

41728

Ashkenazi Jewish (ASJ)

AF:

0.0846

AC:

2184

AN:

25820

East Asian (EAS)

AF:

0.137

AC:

5360

AN:

39096

South Asian (SAS)

AF:

0.178

AC:

15167

AN:

85050

European-Finnish (FIN)

AF:

0.0661

AC:

3076

AN:

46512

Middle Eastern (MID)

AF:

0.0508

AC:

267

AN:

5252

European-Non Finnish (NFE)

AF:

0.0573

AC:

63251

AN:

1104590

Other (OTH)

AF:

0.0711

AC:

4250

AN:

59814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5158

10316

15474

20632

25790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0709

AC:

10804

AN:

152318

Hom.:

480

Cov.:

AF XY:

0.0744

AC XY:

5543

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0728

AC:

3027

AN:

41572

American (AMR)

AF:

0.0533

AC:

816

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0787

AC:

273

AN:

3470

East Asian (EAS)

AF:

0.173

AC:

894

AN:

5172

South Asian (SAS)

AF:

0.193

AC:

934

AN:

4834

European-Finnish (FIN)

AF:

0.0741

AC:

787

AN:

10618

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0578

AC:

3929

AN:

68026

Other (OTH)

AF:

0.0539

AC:

114

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

543

1085

1628

2170

2713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0627

Hom.:

146

Bravo

AF:

0.0665

Asia WGS

AF:

0.173

AC:

599

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

May 16, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.5

(source)

DANN

Benign

0.80

PhyloP100

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr20-62158616-C-T

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