Variant 19-39308077-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000248668.5(LRFN1):c.1872G>T(p.Lys624Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,505,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

LRFN1
ENST00000248668.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.475

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=0.049093574).

BS2

High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRFN1	NM_020862.2 linkuse as main transcript	c.1872G>T	p.Lys624Asn	missense_variant	5/5	ENST00000248668.5	NP_065913.1	Q9P244
LRFN1	XM_017027033.2 linkuse as main transcript	c.1872G>T	p.Lys624Asn	missense_variant	5/5		XP_016882522.1	Q9P244

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRFN1	ENST00000248668.5 linkuse as main transcript	c.1872G>T	p.Lys624Asn	missense_variant	5/5	1	NM_020862.2	ENSP00000248668.4		Q9P244

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000126

AC:

AN:

1353122

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

664378

show subpopulations

Gnomad4 AFR exome

AF:

0.0000345

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000122

Gnomad4 OTH exome

AF:

0.0000537

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000859

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

Oct 06, 2022

The c.1872G>T (p.K624N) alteration is located in exon 2 (coding exon 2) of the LRFN1 gene. This alteration results from a G to T substitution at nucleotide position 1872, causing the lysine (K) at amino acid position 624 to be replaced by an asparagine (N). 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

0.20

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.013

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.57

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.030

REVEL

Benign

0.025

Sift

Benign

0.38

Sift4G

Benign

0.44

Polyphen

0.28

Vest4

0.061

MutPred

0.30

Loss of ubiquitination at K624 (P = 0.0019);

MVP

0.10

ClinPred

0.024

GERP RS

1.9

Varity_R

0.058

gMVP

0.17

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