Variant 1-53962299-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001256409.2(LRRC42):c.817A>G(p.Ile273Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

LRRC42
NM_001256409.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0100

Variant links:

Genes affected

LRRC42 (HGNC:28792): (leucine rich repeat containing 42)

LRRC42 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026225328).

BP6

Variant 1-53962299-A-G is Benign according to our data. Variant chr1-53962299-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3120710.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC42	NM_001256409.2 linkuse as main transcript	c.817A>G	p.Ile273Val	missense_variant	7/9	ENST00000371370.8	NP_001243338.1
LRRC42	NM_052940.5 linkuse as main transcript	c.817A>G	p.Ile273Val	missense_variant	6/8		NP_443172.1
LRRC42	XM_006710328.5 linkuse as main transcript	c.817A>G	p.Ile273Val	missense_variant	7/9		XP_006710391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LRRC42	ENST00000371370.8 linkuse as main transcript	c.817A>G	p.Ile273Val	missense_variant	7/9	2	NM_001256409.2	ENSP00000360421	P1
LRRC42	ENST00000319223.8 linkuse as main transcript	c.817A>G	p.Ile273Val	missense_variant	6/8	1		ENSP00000318185	P1
LRRC42	ENST00000713564.1 linkuse as main transcript	c.817A>G	p.Ile273Val	missense_variant	7/9			ENSP00000518857	P1
LRRC42	ENST00000477905.1 linkuse as main transcript	n.347A>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251380

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460536

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726678

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000761

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.31

DANN

Benign

0.28

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.54

.;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.026

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.14

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.040

N;N

REVEL

Benign

0.015

Sift

Benign

0.45

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.0

B;B

Vest4

0.10

MutPred

0.31

Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);

MVP

0.12

MPC

0.055

ClinPred

0.015

GERP RS

-0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.013

gMVP

0.35

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