20-62161393-G-A

Position:

• chr20-62161393-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198935.3(SS18L1):​c.232-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 1,612,178 control chromosomes in the GnomAD database, including 3,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (692 hom., cov: 32)
  • Exomes 𝑓: 0.052 (2350 hom.)
• Consequence: SS18L1 NM_198935.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0300

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 20-62161393-G-A is Benign according to our data. Variant chr20-62161393-G-A is described in ClinVar as [Benign]. Clinvar id is 1245616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SS18L1	NM_198935.3	c.232-43G>A		intron_variant		ENST00000331758.8	NP_945173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SS18L1	ENST00000331758.8	c.232-43G>A		intron_variant		1	NM_198935.3	ENSP00000333012.3
SS18L1	ENST00000450482.5	c.241-43G>A		intron_variant		5		ENSP00000398634.1
SS18L1	ENST00000370848.8	c.-58G>A		upstream_gene_variant		1		ENSP00000359885.5

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11812 AN: 151702 Hom.: 689 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.000777

Gnomad SAS AF: 0.0480

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0506

Gnomad OTH AF: 0.0897

GnomAD3 exomes AF: 0.0508 AC: 12458 AN: 245030 Hom.: 509 AF XY: 0.0499 AC XY: 6688 AN XY: 134064

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.0371

Gnomad ASJ exome AF: 0.0978

Gnomad EAS exome AF: 0.000946

Gnomad SAS exome AF: 0.0471

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.0516

Gnomad OTH exome AF: 0.0526

GnomAD4 exome AF: 0.0516 AC: 75294 AN: 1460358 Hom.: 2350 Cov.: 32 AF XY: 0.0513 AC XY: 37280 AN XY: 726470

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.0396

Gnomad4 ASJ exome AF: 0.0945

Gnomad4 EAS exome AF: 0.000705

Gnomad4 SAS exome AF: 0.0463

Gnomad4 FIN exome AF: 0.0216

Gnomad4 NFE exome AF: 0.0508

Gnomad4 OTH exome AF: 0.0574

GnomAD4 genome AF: 0.0780 AC: 11835 AN: 151820 Hom.: 692 Cov.: 32 AF XY: 0.0749 AC XY: 5557 AN XY: 74158

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0517

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.000584

Gnomad4 SAS AF: 0.0485

Gnomad4 FIN AF: 0.0189

Gnomad4 NFE AF: 0.0506

Gnomad4 OTH AF: 0.0888

Alfa AF: 0.0503 Hom.: 79

Bravo AF: 0.0839

Asia WGS AF: 0.0380 AC: 135 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs60991008; hg19: chr20-60736449;