chr6-18120937-G-A

Variant names:

• chr6-18120937-G-A
• rs114713758
• NM_198586.3:c.*482C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198586.3(NHLRC1):​c.*482C>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 0.000065 in 184,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: NHLRC1 NM_198586.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Lafora disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198586.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHLRC1	NM_198586.3	MANE Select	c.*482C>T		3_prime_UTR	Exon 1 of 1	NP_940988.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHLRC1	ENST00000340650.6	TSL:6 MANE Select	c.*482C>T		3_prime_UTR	Exon 1 of 1	ENSP00000345464.3	Q6VVB1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000308 AC: 1 AN: 32484 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 17070

African (AFR) AF: 0.00 AC: 0 AN: 572

American (AMR) AF: 0.00 AC: 0 AN: 3278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 504

East Asian (EAS) AF: 0.00 AC: 0 AN: 1992

South Asian (SAS) AF: 0.00 AC: 0 AN: 4118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 96

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 19336

Other (OTH) AF: 0.000618 AC: 1 AN: 1618

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152174 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74348

African (AFR) AF: 0.000266 AC: 11 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.63
DANN	Benign	0.17
PhyloP100		-0.88

Splicing

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

Other links and lift over

dbSNP: rs114713758; hg19: chr6-18121168;