Variant 12-132604530-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001195520.2(LRCOL1):c.286C>T(p.Arg96Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000877 in 1,536,140 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00042 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00093 ( 1 hom. )

Consequence

LRCOL1
NM_001195520.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.80

Variant links:

Genes affected

LRCOL1 (HGNC:44160): (leucine rich colipase like 1) Predicted to enable enzyme activator activity. Predicted to be involved in response to food. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LRCOL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04658717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRCOL1	NM_001195520.2 linkuse as main transcript	c.286C>T	p.Arg96Cys	missense_variant	4/6	ENST00000376608.9	NP_001182449.1	A6NCL2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRCOL1	ENST00000376608.9 linkuse as main transcript	c.286C>T	p.Arg96Cys	missense_variant	4/6	1	NM_001195520.2	ENSP00000479730.1		A6NCL2

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.000691

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000511

AC:

AN:

137044

Hom.:

AF XY:

0.000497

AC XY:

AN XY:

74470

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000981

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:

0.000782

Gnomad OTH exome

AF:

0.000952

GnomAD4 exome

AF:

0.000927

AC:

1283

AN:

1383824

Hom.:

Cov.:

AF XY:

0.000942

AC XY:

643

AN XY:

682840

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.00104

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000147

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.000725

GnomAD4 genome

AF:

0.000420

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000287

Hom.:

Bravo

AF:

0.000540

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.0000472

AC:

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 06, 2021

The c.286C>T (p.R96C) alteration is located in exon 4 (coding exon 3) of the LRCOL1 gene. This alteration results from a C to T substitution at nucleotide position 286, causing the arginine (R) at amino acid position 96 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

-0.35

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.095

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.55

MetaRNN

Benign

0.047

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.24

Sift4G

Benign

0.080

Vest4

0.14

MVP

0.39

GERP RS

-3.4

Varity_R

0.12

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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