Variant chr14-41887066-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_152447.5(LRFN5):c.441C>T(p.Phe147=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,614,038 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0081 ( 7 hom., cov: 32)

Exomes 𝑓: 0.012 ( 145 hom. )

Consequence

LRFN5
NM_152447.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.722

Variant links:

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]

LRFN5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 14-41887066-C-T is Benign according to our data. Variant chr14-41887066-C-T is described in ClinVar as [Benign]. Clinvar id is 3042008.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.722 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0115 (16821/1461742) while in subpopulation SAS AF= 0.0167 (1437/86254). AF 95% confidence interval is 0.0159. There are 145 homozygotes in gnomad4_exome. There are 8542 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1231 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRFN5	NM_152447.5 linkuse as main transcript	c.441C>T	p.Phe147=	synonymous_variant	3/6	ENST00000298119.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRFN5	ENST00000298119.9 linkuse as main transcript	c.441C>T	p.Phe147=	synonymous_variant	3/6	1	NM_152447.5	P3
LRFN5	ENST00000554171.1 linkuse as main transcript	c.441C>T	p.Phe147=	synonymous_variant	5/7	1		A1
LRFN5	ENST00000554120.5 linkuse as main transcript	c.441C>T	p.Phe147=	synonymous_variant	3/4	5		A1

Frequencies

GnomAD3 genomes

AF:

0.00809

AC:

1231

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0155

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00940

AC:

2362

AN:

251242

Hom.:

AF XY:

0.0104

AC XY:

1417

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.0145

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0170

Gnomad FIN exome

AF:

0.00562

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00832

GnomAD4 exome

AF:

0.0115

AC:

16821

AN:

1461742

Hom.:

145

Cov.:

AF XY:

0.0117

AC XY:

8542

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.0158

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0167

Gnomad4 FIN exome

AF:

0.00587

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.00808

AC:

1231

AN:

152296

Hom.:

Cov.:

AF XY:

0.00756

AC XY:

563

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00245

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0157

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.0110

Hom.:

Bravo

AF:

0.00711

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0131

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

LRFN5-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.73

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

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