rs58316174

Variant names:

• chr20-62161244-C-A
• rs58316174
• NM_198935.3:c.232-192C>A

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.232-192C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 150,966 control chromosomes in the GnomAD database, including 409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.065 (409 hom., cov: 31)
• Consequence: SS18L1 NM_198935.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19
• Publications: 1 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=-0.91).
• BP6: Variant 20-62161244-C-A is Benign according to our data. Variant chr20-62161244-C-A is described in ClinVar as [Benign]. Clinvar id is 1249187.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SS18L1	NM_198935.3	c.232-192C>A		intron_variant	Intron 3 of 10	ENST00000331758.8	NP_945173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SS18L1	ENST00000331758.8	c.232-192C>A		intron_variant	Intron 3 of 10	1	NM_198935.3	ENSP00000333012.3
SS18L1	ENST00000450482.5	c.241-192C>A		intron_variant	Intron 4 of 4	5		ENSP00000398634.1
SS18L1	ENST00000370848.8	c.-207C>A		upstream_gene_variant		1		ENSP00000359885.5

Frequencies

GnomAD3 genomes AF: 0.0646 AC: 9745 AN: 150848 Hom.: 408 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0471

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.000778

Gnomad SAS AF: 0.0480

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0505

Gnomad OTH AF: 0.0791

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

GnomAD4 genome AF: 0.0646 AC: 9759 AN: 150966 Hom.: 409 Cov.: 31 AF XY: 0.0626 AC XY: 4612 AN XY: 73668

African (AFR) AF: 0.112 AC: 4604 AN: 41060

American (AMR) AF: 0.0470 AC: 712 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3466

East Asian (EAS) AF: 0.000585 AC: 3 AN: 5132

South Asian (SAS) AF: 0.0485 AC: 219 AN: 4516

European-Finnish (FIN) AF: 0.0186 AC: 196 AN: 10516

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0505 AC: 3425 AN: 67846

Other (OTH) AF: 0.0783 AC: 163 AN: 2082

Alfa AF: 0.0657 Hom.: 44

Bravo AF: 0.0699

Asia WGS AF: 0.0350 AC: 124 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.91
CADD	Benign	0.33
DANN	Benign	0.61
PhyloP100		-1.2
PromoterAI		-0.016	Neutral
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: rs58316174; hg19: chr20-60736300;