Variant 6-18120793-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_198586.3(NHLRC1):c.*626C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0582 in 153,520 control chromosomes in the GnomAD database, including 324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.058 ( 323 hom., cov: 33)

Exomes 𝑓: 0.028 ( 1 hom. )

Consequence

NHLRC1
NM_198586.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.606

Variant links:

Genes affected

NHLRC1 (HGNC:21576): (NHL repeat containing E3 ubiquitin protein ligase 1) The protein encoded by this gene is a single subunit E3 ubiquitin ligase. Laforin is polyubiquitinated by the encoded protein. Defects in this intronless gene lead to an accumulation of laforin and onset of Lafora disease, also known as progressive myoclonic epilepsy type 2 (EPM2).[provided by RefSeq, Mar 2010]

NHLRC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 6-18120793-G-A is Benign according to our data. Variant chr6-18120793-G-A is described in ClinVar as [Benign]. Clinvar id is 356062.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-18120793-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHLRC1	NM_198586.3 linkuse as main transcript	c.*626C>T		3_prime_UTR_variant	1/1	ENST00000340650.6	NP_940988.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHLRC1	ENST00000340650.6 linkuse as main transcript	c.*626C>T		3_prime_UTR_variant	1/1		NM_198586.3	ENSP00000345464	P1

Frequencies

GnomAD3 genomes

AF:

0.0584

AC:

8887

AN:

152116

Hom.:

323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0557

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.0134

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.0294

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0424

Gnomad OTH

AF:

0.0561

GnomAD4 exome

AF:

0.0280

AC:

AN:

1286

Hom.:

Cov.:

AF XY:

0.0291

AC XY:

AN XY:

652

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0236

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0324

Gnomad4 OTH exome

AF:

0.0294

GnomAD4 genome

AF:

0.0585

AC:

8903

AN:

152234

Hom.:

323

Cov.:

AF XY:

0.0570

AC XY:

4239

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.0556

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.0135

Gnomad4 SAS

AF:

0.0185

Gnomad4 FIN

AF:

0.0294

Gnomad4 NFE

AF:

0.0424

Gnomad4 OTH

AF:

0.0555

Alfa

AF:

0.0497

Hom.:

Bravo

AF:

0.0632

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lafora disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.4

DANN

Benign

0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over