Genetic Variant SS18L1:c.70-56C>T (chr20-62158616-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

Gnomad4 AFR exome

AF:

0.0716

Gnomad4 AMR exome

AF:

0.0488

Gnomad4 ASJ exome

AF:

0.0846

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.0661

Gnomad4 NFE exome

AF:

0.0573

Gnomad4 OTH exome

AF:

0.0711

GnomAD4 genome

AF:

0.0709

AC:

10804

AN:

152318

Hom.:

480

Cov.:

AF XY:

0.0744

AC XY:

5543

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0728

Gnomad4 AMR

AF:

0.0533

Gnomad4 ASJ

AF:

0.0787

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.0741

Gnomad4 NFE

AF:

0.0578

Gnomad4 OTH

AF:

0.0539

Alfa

AF:

0.0640

Hom.:

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

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

-0.87

CADD

Benign

5.5

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over