Variant 7-16566397-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001195280.2(LRRC72):c.512G>A(p.Arg171Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000596 in 1,540,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 0 hom. )

Consequence

LRRC72
NM_001195280.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Variant links:

Genes affected

LRRC72 (HGNC:42972): (leucine rich repeat containing 72)

LRRC72 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=0.046313822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC72	NM_001195280.2 linkuse as main transcript	c.512G>A	p.Arg171Gln	missense_variant	6/9	ENST00000401542.3
LRRC72	XM_011515057.2 linkuse as main transcript	c.512G>A	p.Arg171Gln	missense_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC72	ENST00000401542.3 linkuse as main transcript	c.512G>A	p.Arg171Gln	missense_variant	6/9	5	NM_001195280.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

152120

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000335

AC:

AN:

143208

Hom.:

AF XY:

0.000311

AC XY:

AN XY:

77138

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000176

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:

0.000749

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.000615

AC:

853

AN:

1388092

Hom.:

Cov.:

AF XY:

0.000570

AC XY:

390

AN XY:

684594

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000282

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000208

Gnomad4 NFE exome

AF:

0.000752

Gnomad4 OTH exome

AF:

0.000573

GnomAD4 genome

AF:

0.000427

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74422

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:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000671

Hom.:

Bravo

AF:

0.000340

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000215

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

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

Dec 15, 2022

The c.512G>A (p.R171Q) alteration is located in exon 6 (coding exon 6) of the LRRC72 gene. This alteration results from a G to A substitution at nucleotide position 512, causing the arginine (R) at amino acid position 171 to be replaced by a glutamine (Q). 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

0.080

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.62

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.015

Eigen

Benign

0.16

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.66

M_CAP

Benign

0.0089

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.17

Sift

Benign

0.14

Sift4G

Uncertain

0.018

Vest4

0.077

MVP

0.33

ClinPred

0.11

GERP RS

3.6

Varity_R

0.074

gMVP

0.29

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