20-62159697-A-G

Variant names:

• chr20-62159697-A-G
• rs55818729
• NM_198935.3:c.147-180A>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.147-180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,926 control chromosomes in the GnomAD database, including 10,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (10708 hom., cov: 30)
• Consequence: SS18L1 NM_198935.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.37
• 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=-0.9).
• BP6: Variant 20-62159697-A-G is Benign according to our data. Variant chr20-62159697-A-G is described in ClinVar as [Benign]. Clinvar id is 1228888.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SS18L1	NM_198935.3	c.147-180A>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.147-180A>G		intron_variant	Intron 2 of 10	1	NM_198935.3	ENSP00000333012.3
SS18L1	ENST00000450482.5	c.156-180A>G		intron_variant	Intron 3 of 4	5		ENSP00000398634.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42529 AN: 151808 Hom.: 10670 Cov.: 30

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.0518

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.281 AC: 42625 AN: 151926 Hom.: 10708 Cov.: 30 AF XY: 0.277 AC XY: 20565 AN XY: 74274

African (AFR) AF: 0.678 AC: 28069 AN: 41426

American (AMR) AF: 0.161 AC: 2465 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3462

East Asian (EAS) AF: 0.174 AC: 894 AN: 5142

South Asian (SAS) AF: 0.248 AC: 1193 AN: 4812

European-Finnish (FIN) AF: 0.0945 AC: 998 AN: 10562

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7724 AN: 67934

Other (OTH) AF: 0.231 AC: 487 AN: 2110

Alfa AF: 0.0848 Hom.: 238

Bravo AF: 0.300

Asia WGS AF: 0.243 AC: 844 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 15, 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	-0.90
CADD	Benign	0.14
DANN	Benign	0.37
PhyloP100		-2.4
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: rs55818729; hg19: chr20-60734753;