Variant 6-53899787-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018214.5(LRRC1):c.683C>G(p.Ser228Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000359 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

LRRC1
NM_018214.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.56

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC1	NM_018214.5 linkuse as main transcript	c.683C>G	p.Ser228Cys	missense_variant	8/14	ENST00000370888.6	NP_060684.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC1	ENST00000370888.6 linkuse as main transcript	c.683C>G	p.Ser228Cys	missense_variant	8/14	1	NM_018214.5	ENSP00000359925	P1	Q9BTT6-1
LRRC1	ENST00000487251.5 linkuse as main transcript	c.*85C>G		3_prime_UTR_variant, NMD_transcript_variant	9/11	2		ENSP00000435217		Q9BTT6-2

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000212

AC:

AN:

249520

Hom.:

AF XY:

0.000229

AC XY:

AN XY:

135378

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000433

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000367

AC:

536

AN:

1461816

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

248

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000471

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000283

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000408

Hom.:

Bravo

AF:

0.000234

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000490

AC:

ExAC

AF:

0.000207

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000534

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 26, 2022

The c.683C>G (p.S228C) alteration is located in exon 8 (coding exon 8) of the LRRC1 gene. This alteration results from a C to G substitution at nucleotide position 683, causing the serine (S) at amino acid position 228 to be replaced by a cysteine (C). 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

Pathogenic

0.69

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.063

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.51

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.61

Sift

Benign

0.043

Sift4G

Uncertain

0.047

Polyphen

1.0

Vest4

0.73

MVP

0.26

MPC

1.1

ClinPred

0.61

GERP RS

5.6

Varity_R

0.60

gMVP

0.72

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