Variant 19-39307901-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020862.2(LRFN1):c.2048C>T(p.Ala683Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,564,852 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

LRFN1
NM_020862.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Variant links:

Genes affected

LRFN1 (HGNC:29290): (leucine rich repeat and fibronectin type III domain containing 1) Predicted to be involved in regulation of postsynaptic density assembly. Predicted to be located in plasma membrane. Predicted to be active in cell surface. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRFN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034009308).

BS2

High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRFN1	NM_020862.2 linkuse as main transcript	c.2048C>T	p.Ala683Val	missense_variant	5/5	ENST00000248668.5	NP_065913.1
LRFN1	XM_017027033.2 linkuse as main transcript	c.2048C>T	p.Ala683Val	missense_variant	5/5		XP_016882522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRFN1	ENST00000248668.5 linkuse as main transcript	c.2048C>T	p.Ala683Val	missense_variant	5/5	1	NM_020862.2	ENSP00000248668	P1

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000229

AC:

AN:

174396

Hom.:

AF XY:

0.000245

AC XY:

AN XY:

97794

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000715

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000296

Gnomad OTH exome

AF:

0.000425

GnomAD4 exome

AF:

0.000161

AC:

227

AN:

1412624

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

106

AN XY:

700130

show subpopulations

Gnomad4 AFR exome

AF:

0.0000321

Gnomad4 AMR exome

AF:

0.0000501

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000380

Gnomad4 FIN exome

AF:

0.0000256

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.000255

GnomAD4 genome

AF:

0.000177

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000269

Hom.:

Bravo

AF:

0.000181

ExAC

AF:

0.000136

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.2048C>T (p.A683V) alteration is located in exon 2 (coding exon 2) of the LRFN1 gene. This alteration results from a C to T substitution at nucleotide position 2048, causing the alanine (A) at amino acid position 683 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.75

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

MutationTaster

Benign

0.92

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.52

REVEL

Benign

0.088

Sift

Benign

0.077

Sift4G

Benign

0.19

Polyphen

0.062

Vest4

0.16

MutPred

0.19

Loss of glycosylation at P684 (P = 0.0766);

MVP

0.13

ClinPred

0.014

GERP RS

3.4

Varity_R

0.048

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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