NM_198935.3:c.376+175C>A

Variant names:

• chr20-62161755-C-A
• rs6121520
• NM_198935.3:c.376+175C>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.376+175C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,306 control chromosomes in the GnomAD database, including 2,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (2526 hom., cov: 33)
• Consequence: SS18L1 NM_198935.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.57
• 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: ClinGen, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-62161755-C-A is Benign according to our data. Variant chr20-62161755-C-A is described in ClinVar as Benign. ClinVar VariationId is 1220783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 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.376+175C>A		intron	N/A	NP_945173.1	O75177-1
	SS18L1	NM_001301778.2		c.-18+175C>A		intron	N/A	NP_001288707.1	O75177-4
	SS18L1	NR_125980.3		n.807+175C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SS18L1	ENST00000331758.8	TSL:1 MANE Select	c.376+175C>A		intron	N/A	ENSP00000333012.3	O75177-1
	SS18L1	ENST00000370848.8	TSL:1	c.130+175C>A		intron	N/A	ENSP00000359885.5	O75177-3
	SS18L1	ENST00000450482.5	TSL:5	c.*175C>A		downstream_gene	N/A	ENSP00000398634.1	Q9BR54

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15530 AN: 152188 Hom.: 2525 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0417

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00461

Gnomad OTH AF: 0.0716

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

GnomAD4 genome AF: 0.102 AC: 15570 AN: 152306 Hom.: 2526 Cov.: 33 AF XY: 0.0988 AC XY: 7361 AN XY: 74468

African (AFR) AF: 0.347 AC: 14396 AN: 41526

American (AMR) AF: 0.0416 AC: 637 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00462 AC: 314 AN: 68032

Other (OTH) AF: 0.0709 AC: 150 AN: 2116

Alfa AF: 0.00440 Hom.: 6

Bravo AF: 0.117

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.23
DANN	Benign	0.75
PhyloP100		-1.6
PromoterAI		0.011	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: rs6121520; hg19: chr20-60736811;