Variant 6-53897294-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018214.5(LRRC1):c.577A>T(p.Ile193Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000311 in 1,609,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I193V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

LRRC1
NM_018214.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.53

Variant links:

Genes affected

LRRC1 (HGNC:14307): (leucine rich repeat containing 1) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LRRC1 links:

LRRC1 (HGNC:):

LRRC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16087198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC1	NM_018214.5 linkuse as main transcript	c.577A>T	p.Ile193Phe	missense_variant	7/14	ENST00000370888.6	NP_060684.4	Q9BTT6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC1	ENST00000370888.6 linkuse as main transcript	c.577A>T	p.Ile193Phe	missense_variant	7/14	1	NM_018214.5	ENSP00000359925.1		Q9BTT6-1
LRRC1	ENST00000487251.5 linkuse as main transcript	n.573A>T		non_coding_transcript_exon_variant	8/11	2		ENSP00000435217.1		Q9BTT6-2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

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:

0.00

GnomAD3 exomes

AF:

0.0000520

AC:

AN:

249814

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135090

show subpopulations

Gnomad AFR exome

AF:

0.000679

Gnomad AMR exome

AF:

0.0000583

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:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1457170

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725138

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.0000672

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:

0.0000498

GnomAD4 genome

AF:

0.000151

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000505

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:

0.00

ExAC

AF:

0.0000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.77

M_CAP

Benign

0.022

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.25

Sift

Benign

0.080

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.36

MutPred

0.44

Loss of helix (P = 0.0376);

MVP

0.14

MPC

1.4

ClinPred

0.13

GERP RS

3.9

Varity_R

0.36

gMVP

0.63

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over