20-62158583-A-G

Variant names:

• chr20-62158583-A-G
• rs6142963
• NM_198935.3:c.70-89A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198935.3(SS18L1):​c.70-89A>G 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 1,542,584 control chromosomes in the GnomAD database, including 4,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (491 hom., cov: 32)
  • Exomes 𝑓: 0.068 (4249 hom.)
• Consequence: SS18L1 NM_198935.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.76
• Publications: 5 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: ClinGen, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 20-62158583-A-G is Benign according to our data. Variant chr20-62158583-A-G is described in ClinVar as Benign. ClinVar VariationId is 1182966.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198935.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SS18L1	NM_198935.3	MANE Select	c.70-89A>G		intron	N/A	NP_945173.1	O75177-1
	SS18L1	NM_001301778.2		c.-244-89A>G		intron	N/A	NP_001288707.1	O75177-4
	SS18L1	NR_125980.3		n.307-89A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SS18L1	ENST00000331758.8	TSL:1 MANE Select	c.70-89A>G		intron	N/A	ENSP00000333012.3	O75177-1
	SS18L1	ENST00000450482.5	TSL:5	c.-116-89A>G		intron	N/A	ENSP00000398634.1	Q9BR54

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10894 AN: 152166 Hom.: 490 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0786

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: 0.0516

GnomAD4 exome AF: 0.0680 AC: 94471 AN: 1390300 Hom.: 4249 AF XY: 0.0716 AC XY: 49156 AN XY: 686712

African (AFR) AF: 0.0753 AC: 2397 AN: 31848

American (AMR) AF: 0.0489 AC: 1787 AN: 36546

Ashkenazi Jewish (ASJ) AF: 0.0849 AC: 2132 AN: 25120

East Asian (EAS) AF: 0.136 AC: 5006 AN: 36716

South Asian (SAS) AF: 0.178 AC: 14498 AN: 81332

European-Finnish (FIN) AF: 0.0674 AC: 2632 AN: 39042

Middle Eastern (MID) AF: 0.0495 AC: 220 AN: 4440

European-Non Finnish (NFE) AF: 0.0572 AC: 61660 AN: 1077284

Other (OTH) AF: 0.0714 AC: 4139 AN: 57972

GnomAD4 genome AF: 0.0716 AC: 10908 AN: 152284 Hom.: 491 Cov.: 32 AF XY: 0.0751 AC XY: 5591 AN XY: 74456

African (AFR) AF: 0.0753 AC: 3129 AN: 41560

American (AMR) AF: 0.0534 AC: 817 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0786 AC: 273 AN: 3472

East Asian (EAS) AF: 0.173 AC: 895 AN: 5178

South Asian (SAS) AF: 0.193 AC: 933 AN: 4824

European-Finnish (FIN) AF: 0.0741 AC: 786 AN: 10606

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0578 AC: 3930 AN: 68022

Other (OTH) AF: 0.0543 AC: 115 AN: 2116

Alfa AF: 0.0615 Hom.: 580

Bravo AF: 0.0674

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.066
DANN	Benign	0.069
PhyloP100		-1.8
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: rs6142963; hg19: chr20-60733639; COSMIC: COSV107389488; COSMIC: COSV107389488;