rs61422126

Variant names:

• chr20-62161411-C-T
• rs61422126
• NM_198935.3:c.232-25C>T

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.232-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,612,580 control chromosomes in the GnomAD database, including 1,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (769 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (690 hom.)
• Consequence: SS18L1 NM_198935.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.205
• 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: Genomics England PanelApp, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 20-62161411-C-T is Benign according to our data. Variant chr20-62161411-C-T is described in ClinVar as [Benign]. Clinvar id is 1222437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SS18L1	NM_198935.3	c.232-25C>T		intron_variant	Intron 3 of 10	ENST00000331758.8	NP_945173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SS18L1	ENST00000331758.8	c.232-25C>T		intron_variant	Intron 3 of 10	1	NM_198935.3	ENSP00000333012.3
SS18L1	ENST00000450482.5	c.241-25C>T		intron_variant	Intron 4 of 4	5		ENSP00000398634.1
SS18L1	ENST00000370848.8	c.-40C>T		upstream_gene_variant		1		ENSP00000359885.5

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8308 AN: 151872 Hom.: 770 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000626

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0374

GnomAD2 exomes AF: 0.0141 AC: 3494 AN: 247658 AF XY: 0.0106

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.00948

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000611

Gnomad OTH exome AF: 0.00727

GnomAD4 exome AF: 0.00573 AC: 8365 AN: 1460590 Hom.: 690 Cov.: 31 AF XY: 0.00501 AC XY: 3637 AN XY: 726594

African (AFR) AF: 0.197 AC: 6581 AN: 33478

American (AMR) AF: 0.0110 AC: 493 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000452 AC: 39 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52200

Middle Eastern (MID) AF: 0.0101 AC: 58 AN: 5766

European-Non Finnish (NFE) AF: 0.000383 AC: 426 AN: 1111978

Other (OTH) AF: 0.0127 AC: 768 AN: 60380

GnomAD4 genome AF: 0.0547 AC: 8315 AN: 151990 Hom.: 769 Cov.: 32 AF XY: 0.0520 AC XY: 3864 AN XY: 74280

African (AFR) AF: 0.190 AC: 7857 AN: 41414

American (AMR) AF: 0.0219 AC: 334 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000626 AC: 3 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 67968

Other (OTH) AF: 0.0370 AC: 78 AN: 2108

Alfa AF: 0.0255 Hom.: 111

Bravo AF: 0.0632

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 25, 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	-0.81
CADD	Benign	1.7
DANN	Benign	0.78
PhyloP100		-0.20
PromoterAI		0.019	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: rs61422126; hg19: chr20-60736467; COSMIC: COSV59212458; COSMIC: COSV59212458;