Variant 3-194359595-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_130830.5(LRRC15):c.1449T>A(p.Ser483Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000638 in 1,613,838 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 6 hom. )

Consequence

LRRC15
NM_130830.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.228

Variant links:

Genes affected

LRRC15 (HGNC:20818): (leucine rich repeat containing 15) Enables collagen binding activity; fibronectin binding activity; and laminin binding activity. Involved in negative regulation of protein localization to plasma membrane; positive regulation of cell migration; and receptor-mediated virion attachment to host cell. Located in extracellular exosome. Colocalizes with collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

LRRC15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004420817).

BP6

Variant 3-194359595-A-T is Benign according to our data. Variant chr3-194359595-A-T is described in ClinVar as [Benign]. Clinvar id is 786028.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 528 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC15	NM_130830.5 link	c.1449T>A	p.Ser483Arg	missense_variant	2/2	ENST00000347624.4	NP_570843.2	Q8TF66-1B3KWI4
LRRC15	NM_001135057.3 link	c.1467T>A	p.Ser489Arg	missense_variant	3/3		NP_001128529.2	Q8TF66-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC15	ENST00000347624.4 link	c.1449T>A	p.Ser483Arg	missense_variant	2/2	1	NM_130830.5	ENSP00000306276.4		Q8TF66-1
LRRC15	ENST00000428839.1 link	c.1467T>A	p.Ser489Arg	missense_variant	3/3	1		ENSP00000413707.1		Q8TF66-2

Frequencies

GnomAD3 genomes

AF:

0.00345

AC:

525

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

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:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000844

AC:

211

AN:

250068

Hom.:

AF XY:

0.000636

AC XY:

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.000698

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.000343

AC:

501

AN:

1461502

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

225

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.0121

Gnomad4 AMR exome

AF:

0.000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.000828

GnomAD4 genome

AF:

0.00347

AC:

528

AN:

152336

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

263

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.000915

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:

0.00284

Alfa

AF:

0.000936

Hom.:

Bravo

AF:

0.00395

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00102

AC:

124

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.8

DANN

Benign

0.93

DEOGEN2

Benign

0.064

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.85

N;N

REVEL

Benign

0.019

Sift

Uncertain

0.016

D;D

Sift4G

Benign

0.19

T;T

Polyphen

0.0040

B;B

Vest4

0.11

MutPred

0.35

Loss of glycosylation at S483 (P = 0.003);.;

MVP

0.32

ClinPred

0.0034

GERP RS

2.4

Varity_R

0.067

gMVP

0.28

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