Variant 7-16532519-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001195280.2(LRRC72):c.115T>C(p.Cys39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,550,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

LRRC72
NM_001195280.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.477

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=0.097471476).

BP6

Variant 7-16532519-T-C is Benign according to our data. Variant chr7-16532519-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2355887.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC72	NM_001195280.2 linkuse as main transcript	c.115T>C	p.Cys39Arg	missense_variant	2/9	ENST00000401542.3
LRRC72	XM_011515057.2 linkuse as main transcript	c.115T>C	p.Cys39Arg	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRRC72	ENST00000401542.3 linkuse as main transcript	c.115T>C	p.Cys39Arg	missense_variant	2/9	5	NM_001195280.2	P1
LRRC72	ENST00000482711.1 linkuse as main transcript	n.178T>C		non_coding_transcript_exon_variant	2/3	2
LRRC72	ENST00000382124.7 linkuse as main transcript	c.115T>C	p.Cys39Arg	missense_variant, NMD_transcript_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000333

AC:

AN:

150136

Hom.:

AF XY:

0.0000124

AC XY:

AN XY:

80606

show subpopulations

Gnomad AFR exome

AF:

0.000432

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:

0.00

Gnomad OTH exome

AF:

0.000459

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1397824

Hom.:

Cov.:

AF XY:

0.00000870

AC XY:

AN XY:

689458

show subpopulations

Gnomad4 AFR exome

AF:

0.000412

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.0000690

GnomAD4 genome

AF:

0.000158

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000579

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000989

Hom.:

Bravo

AF:

0.000144

ExAC

AF:

0.0000483

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.63

Cadd

Benign

Dann

Benign

0.67

DEOGEN2

Benign

0.013

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.36

M_CAP

Benign

0.0061

MetaRNN

Benign

0.097

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.99

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.4

REVEL

Benign

0.023

Sift

Benign

0.40

Sift4G

Uncertain

0.015

Vest4

0.23

MVP

0.43

ClinPred

0.020

GERP RS

1.7

Varity_R

0.11

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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