rs75578615

Variant names:

• chr20-62159694-C-G
• rs75578615
• NM_198935.3:c.147-183C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198935.3(SS18L1):​c.147-183C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0335 in 151,068 control chromosomes in the GnomAD database, including 256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.033 (256 hom., cov: 31)
• Consequence: SS18L1 NM_198935.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-62159694-C-G is Benign according to our data. Variant chr20-62159694-C-G is described in ClinVar as [Benign]. Clinvar id is 1236975.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SS18L1	NM_198935.3	c.147-183C>G		intron_variant	Intron 2 of 10	ENST00000331758.8	NP_945173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SS18L1	ENST00000331758.8	c.147-183C>G		intron_variant	Intron 2 of 10	1	NM_198935.3	ENSP00000333012.3
SS18L1	ENST00000450482.5	c.156-183C>G		intron_variant	Intron 3 of 4	5		ENSP00000398634.1

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5041 AN: 150950 Hom.: 255 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00128

Gnomad FIN AF: 0.00143

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00320

Gnomad OTH AF: 0.0222

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

GnomAD4 genome AF: 0.0335 AC: 5056 AN: 151068 Hom.: 256 Cov.: 31 AF XY: 0.0330 AC XY: 2434 AN XY: 73790

African (AFR) AF: 0.110 AC: 4532 AN: 41352

American (AMR) AF: 0.0134 AC: 203 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00128 AC: 6 AN: 4684

European-Finnish (FIN) AF: 0.00143 AC: 15 AN: 10520

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00320 AC: 216 AN: 67516

Other (OTH) AF: 0.0220 AC: 46 AN: 2090

Alfa AF: 0.0214 Hom.: 25

Bravo AF: 0.0376

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 21, 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	-0.85
CADD	Benign	4.7
DANN	Benign	0.56
PhyloP100		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs75578615; hg19: chr20-60734750;