chr14-41842228-T-C

Variant names:

• chr14-41842228-T-C
• rs12878452
• NM_152447.5:c.-20-44378T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152447.5(LRFN5):​c.-20-44378T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,018 control chromosomes in the GnomAD database, including 2,599 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 0.18 (2599 hom., cov: 32)
• Consequence: LRFN5 NM_152447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRFN5	NM_152447.5	c.-20-44378T>C		intron_variant	Intron 2 of 5	ENST00000298119.9	NP_689660.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRFN5	ENST00000298119.9	c.-20-44378T>C		intron_variant	Intron 2 of 5	1	NM_152447.5	ENSP00000298119.4
LRFN5	ENST00000554171.1	c.-20-44378T>C		intron_variant	Intron 4 of 6	1		ENSP00000451067.1
LRFN5	ENST00000554120.5	c.-20-44378T>C		intron_variant	Intron 2 of 3	5		ENSP00000451897.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27558 AN: 151900 Hom.: 2593 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.182 AC: 27604 AN: 152018 Hom.: 2599 Cov.: 32 AF XY: 0.176 AC XY: 13112 AN XY: 74298

African (AFR) AF: 0.194 AC: 8069 AN: 41510

American (AMR) AF: 0.191 AC: 2911 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 397 AN: 3470

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5176

South Asian (SAS) AF: 0.140 AC: 675 AN: 4824

European-Finnish (FIN) AF: 0.177 AC: 1875 AN: 10588

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13164 AN: 67866

Other (OTH) AF: 0.163 AC: 343 AN: 2110

Alfa AF: 0.193 Hom.: 463

Bravo AF: 0.187

Asia WGS AF: 0.0800 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.4
DANN	Benign	0.42
PhyloP100		-0.043
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: rs12878452; hg19: chr14-42311431;