Variant 1-3781532-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_020710.3(LRRC47):c.1483G>A(p.Val495Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,866 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LRRC47
NM_020710.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0870

Variant links:

Genes affected

LRRC47 (HGNC:29207): (leucine rich repeat containing 47) Enables RNA binding activity. Predicted to be involved in phenylalanyl-tRNA aminoacylation. [provided by Alliance of Genome Resources, Apr 2022]

LRRC47 links:

LRRC47 (HGNC:):

LRRC47 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07858345).

BP6

Variant 1-3781532-C-T is Benign according to our data. Variant chr1-3781532-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3120760.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC47	NM_020710.3 linkuse as main transcript	c.1483G>A	p.Val495Ile	missense_variant	6/7	ENST00000378251.3	NP_065761.1	Q8N1G4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRC47	ENST00000378251.3 linkuse as main transcript	c.1483G>A	p.Val495Ile	missense_variant	6/7	1	NM_020710.3	ENSP00000367498.1	Q8N1G4
LRRC47	ENST00000462356.5 linkuse as main transcript	n.353G>A		non_coding_transcript_exon_variant	3/4	2
LRRC47	ENST00000479239.1 linkuse as main transcript	n.*215G>A		non_coding_transcript_exon_variant	4/5	3		ENSP00000462103.1	J3KRP5
LRRC47	ENST00000479239.1 linkuse as main transcript	n.*215G>A		3_prime_UTR_variant	4/5	3		ENSP00000462103.1	J3KRP5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461664

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000416

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

Jan 02, 2024

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

0.078

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.5

DANN

Benign

0.79

DEOGEN2

Benign

0.043

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.73

M_CAP

Benign

0.017

MetaRNN

Benign

0.079

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.86

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.67

REVEL

Benign

0.063

Sift

Benign

0.38

Sift4G

Benign

0.26

Polyphen

0.039

Vest4

0.14

MutPred

0.59

Loss of ubiquitination at K493 (P = 0.1423);

MVP

0.13

MPC

0.25

ClinPred

0.10

GERP RS

-0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.063

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