Variant 6-18120937-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_198586.3(NHLRC1):c.*482C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 184,758 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 61 hom., cov: 33)

Exomes 𝑓: 0.024 ( 12 hom. )

Consequence

NHLRC1
NM_198586.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.879

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 6-18120937-G-C is Benign according to our data. Variant chr6-18120937-G-C is described in ClinVar as [Benign]. Clinvar id is 356064.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0208 (3163/152286) while in subpopulation AMR AF= 0.043 (658/15292). AF 95% confidence interval is 0.0403. There are 61 homozygotes in gnomad4. There are 1481 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHLRC1	NM_198586.3 linkuse as main transcript	c.*482C>G		3_prime_UTR_variant	1/1	ENST00000340650.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHLRC1	ENST00000340650.6 linkuse as main transcript	c.*482C>G		3_prime_UTR_variant	1/1		NM_198586.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3162

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00497

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0430

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.00616

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.00753

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0279

Gnomad OTH

AF:

0.0335

GnomAD4 exome

AF:

0.0240

AC:

780

AN:

32472

Hom.:

Cov.:

AF XY:

0.0226

AC XY:

386

AN XY:

17066

show subpopulations

Gnomad4 AFR exome

AF:

0.00350

Gnomad4 AMR exome

AF:

0.0528

Gnomad4 ASJ exome

AF:

0.0199

Gnomad4 EAS exome

AF:

0.0136

Gnomad4 SAS exome

AF:

0.0189

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.0227

Gnomad4 OTH exome

AF:

0.0241

GnomAD4 genome

AF:

0.0208

AC:

3163

AN:

152286

Hom.:

Cov.:

AF XY:

0.0199

AC XY:

1481

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00496

Gnomad4 AMR

AF:

0.0430

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.00598

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.00753

Gnomad4 NFE

AF:

0.0279

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.00574

Hom.:

Bravo

AF:

0.0237

Asia WGS

AF:

0.0150

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 12, 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

-0.97

CADD

Benign

0.20

DANN

Benign

0.27

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