Genetic Variant NM_198935.3:c.232-192C>A (chr20-62161244-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.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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.19

Publications

1 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=-0.91).

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 link	c.232-192C>A		intron_variant	Intron 3 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.232-192C>A	intron_variant	Intron 3 of 10	1	NM_198935.3	ENSP00000333012.3	O75177-1
SS18L1	ENST00000450482.5 link	c.241-192C>A	intron_variant	Intron 4 of 4	5		ENSP00000398634.1	Q9BR54
SS18L1	ENST00000370848.8 link	c.-207C>A	upstream_gene_variant		1		ENSP00000359885.5	O75177-3

Frequencies

GnomAD3 genomes

AF:

0.0646

AC:

9745

AN:

150848

Hom.:

408

Cov.:

show subpopulations

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.:

AF XY:

0.0626

AC XY:

4612

AN XY:

73668

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0505

AC:

3425

AN:

67846

Other (OTH)

AF:

0.0783

AC:

163

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

445

890

1334

1779

2224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0657

Hom.:

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

LINK: link

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

(source)

DANN

Benign

0.61

PhyloP100

-1.2

PromoterAI

-0.016

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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NM_198935.3:c.232-192C>A

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