20-62161244-C-A

Position:

• chr20-62161244-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SS18L1	NM_198935.3	c.232-192C>A		intron_variant		ENST00000331758.8	NP_945173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SS18L1	ENST00000331758.8	c.232-192C>A		intron_variant		1	NM_198935.3	ENSP00000333012.3
SS18L1	ENST00000450482.5	c.241-192C>A		intron_variant		5		ENSP00000398634.1

Frequencies

GnomAD3 genomes AF: 0.0646 AC: 9745 AN: 150848 Hom.: 408 Cov.: 31

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.: 31 AF XY: 0.0626 AC XY: 4612 AN XY: 73668

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0470

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.000585

Gnomad4 SAS AF: 0.0485

Gnomad4 FIN AF: 0.0186

Gnomad4 NFE AF: 0.0505

Gnomad4 OTH AF: 0.0783

Alfa AF: 0.0657 Hom.: 44

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs58316174; hg19: chr20-60736300;