12-132604764-G-C

Position:

• chr12-132604764-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000376608.9(LRCOL1):​c.173C>G​(p.Ala58Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,383,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: LRCOL1 ENST00000376608.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.865

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]

ACMG classification

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=0.047705233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRCOL1	NM_001195520.2	c.173C>G	p.Ala58Gly	missense_variant	3/6	ENST00000376608.9	NP_001182449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRCOL1	ENST00000376608.9	c.173C>G	p.Ala58Gly	missense_variant	3/6	1	NM_001195520.2	ENSP00000479730	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000736 AC: 1 AN: 135782 Hom.: 0 AF XY: 0.0000135 AC XY: 1 AN XY: 73864

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: 0.0000188

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1383876 Hom.: 0 Cov.: 49 AF XY: 0.00000293 AC XY: 2 AN XY: 682882

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: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2023

The c.173C>G (p.A58G) alteration is located in exon 3 (coding exon 2) of the LRCOL1 gene. This alteration results from a C to G substitution at nucleotide position 173, causing the alanine (A) at amino acid position 58 to be replaced by a glycine (G). 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	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	2.5
DANN	Benign	0.40
DEOGEN2	Benign	0.0025	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.048	T
MutationAssessor	Benign	-0.20	N
PrimateAI	Benign	0.27	T
Sift4G	Benign	0.71	T
Vest4		0.10
MVP		0.072
GERP RS		-1.4
Varity_R		0.039
gMVP		0.71

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

Other links and lift over

dbSNP: rs1289401154; hg19: chr12-133181350;