rs58799071

Variant names:

• chr19-35125641-G-A
• rs58799071
• ENST00000587780.5:c.*527C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000587780.5(LGI4):​c.*527C>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 0.00663 in 799,638 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (103 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (32 hom.)
• Consequence: LGI4 ENST00000587780.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.344
• Publications: 0 publications found

Genes affected

LGI4 (HGNC:18712): (leucine rich repeat LGI family member 4) Involved in regulation of myelination. Predicted to be located in extracellular region. Predicted to be active in extracellular space. Implicated in arthrogryposis multiplex congenita-1 and childhood absence epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

FXYD3 (HGNC:4027): (FXYD domain containing ion transport regulator 3) This gene belongs to a small family of FXYD-domain containing regulators of Na+/K+ ATPases which share a 35-amino acid signature sequence domain, beginning with the sequence PFXYD, and containing 7 invariant and 6 highly conserved amino acids. This gene encodes a cell membrane protein that may regulate the function of ion-pumps and ion-channels. This gene may also play a role in tumor progression. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-35125641-G-A is Benign according to our data. Variant chr19-35125641-G-A is described in ClinVar as Benign. ClinVar VariationId is 1281124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000587780.5. 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
	LGI4	NM_139284.3	MANE Select	c.1300-134C>T		intron	N/A	NP_644813.1	Q8N135-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGI4	ENST00000587780.5	TSL:1	c.*527C>T		3_prime_UTR	Exon 6 of 6	ENSP00000467044.2	K7ENQ0
	LGI4	ENST00000310123.8	TSL:1 MANE Select	c.1300-134C>T		intron	N/A	ENSP00000312273.3	Q8N135-1
	LGI4	ENST00000493050.5	TSL:1	n.1359-134C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3200 AN: 152096 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00324 AC: 2097 AN: 647424 Hom.: 32 Cov.: 8 AF XY: 0.00281 AC XY: 954 AN XY: 339018

African (AFR) AF: 0.0681 AC: 1162 AN: 17060

American (AMR) AF: 0.00518 AC: 165 AN: 31830

Ashkenazi Jewish (ASJ) AF: 0.000429 AC: 8 AN: 18640

East Asian (EAS) AF: 0.00 AC: 0 AN: 32196

South Asian (SAS) AF: 0.000544 AC: 32 AN: 58802

European-Finnish (FIN) AF: 0.0000284 AC: 1 AN: 35176

Middle Eastern (MID) AF: 0.00575 AC: 24 AN: 4176

European-Non Finnish (NFE) AF: 0.00116 AC: 481 AN: 416142

Other (OTH) AF: 0.00671 AC: 224 AN: 33402

GnomAD4 genome AF: 0.0211 AC: 3205 AN: 152214 Hom.: 103 Cov.: 32 AF XY: 0.0205 AC XY: 1523 AN XY: 74426

African (AFR) AF: 0.0705 AC: 2925 AN: 41508

American (AMR) AF: 0.0101 AC: 154 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00134 AC: 91 AN: 68006

Other (OTH) AF: 0.0137 AC: 29 AN: 2110

Alfa AF: 0.0169 Hom.: 10

Bravo AF: 0.0253

Asia WGS AF: 0.00404 AC: 15 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.74
PhyloP100		0.34
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: rs58799071; hg19: chr19-35616545;