dbSNP rs6121520: SS18L1:c.376+175C>A (chr20-62161755-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.57

Publications

0 publications found

Variant links:

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

SS18L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SS18L1	NM_198935.3 link	c.376+175C>A		intron_variant	Intron 4 of 10	ENST00000331758.8	NP_945173.1	O75177-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SS18L1	ENST00000331758.8 link	c.376+175C>A	intron_variant	Intron 4 of 10	1	NM_198935.3	ENSP00000333012.3	O75177-1
SS18L1	ENST00000370848.8 link	c.130+175C>A	intron_variant	Intron 1 of 8	1		ENSP00000359885.5	O75177-3
SS18L1	ENST00000450482.5 link	c.*175C>A	downstream_gene_variant		5		ENSP00000398634.1	Q9BR54

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15530

AN:

152188

Hom.:

2525

Cov.:

show subpopulations

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.:

AF XY:

0.0988

AC XY:

7361

AN XY:

74468

show subpopulations

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:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00462

AC:

314

AN:

68032

Other (OTH)

AF:

0.0709

AC:

150

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

564

1128

1691

2255

2819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00440

Hom.:

Bravo

AF:

0.117

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 21, 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

-0.86

CADD

Benign

0.23

(source)

DANN

Benign

0.75

PhyloP100

-1.6

PromoterAI

0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs6121520

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over