rs4143896

Positions:

• chr14-41840400-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000298119.9(LRFN5):​c.-20-46206A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,846 control chromosomes in the GnomAD database, including 19,727 homozygotes. 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 0.50 (19727 hom., cov: 33)
• Consequence: LRFN5 ENST00000298119.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

Genes affected

LRFN5 (HGNC:20360): (leucine rich repeat and fibronectin type III domain containing 5) This gene encodes a protein that belongs to the leucine-rich repeat and fibronectin type III domain-containing family of proteins. A similar protein in mouse, a glycosylated transmembrane protein, is thought to function in presynaptic differentiation. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRFN5	NM_152447.5	c.-20-46206A>T		intron_variant		ENST00000298119.9	NP_689660.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRFN5	ENST00000298119.9	c.-20-46206A>T		intron_variant		1	NM_152447.5	ENSP00000298119	P3
LRFN5	ENST00000554171.1	c.-20-46206A>T		intron_variant		1		ENSP00000451067	A1
LRFN5	ENST00000554120.5	c.-20-46206A>T		intron_variant		5		ENSP00000451897	A1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75396 AN: 151728 Hom.: 19704 Cov.: 33

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.491

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.497 AC: 75468 AN: 151846 Hom.: 19727 Cov.: 33 AF XY: 0.487 AC XY: 36118 AN XY: 74222

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.0746

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.485

Alfa AF: 0.492 Hom.: 2317

Bravo AF: 0.505

Asia WGS AF: 0.220 AC: 764 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.0
DANN	Benign	0.41

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: rs4143896; hg19: chr14-42309603;