Variant chr8-85109759-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033402.5(LRRCC1):c.269G>A(p.Cys90Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0995 in 1,589,296 control chromosomes in the GnomAD database, including 8,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 549 hom., cov: 33)

Exomes 𝑓: 0.10 ( 8007 hom. )

Consequence

LRRCC1
NM_033402.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.40

Variant links:

Genes affected

LRRCC1 (HGNC:29373): (leucine rich repeat and coiled-coil centrosomal protein 1) This gene encodes a centrosomal protein that maintains the structural integrity of the centrosome and plays a key role in mitotic spindle formation. The encoded protein contains an N-terminal leucine-rich repeat domain and a C-terminal coiled-coil domain. It associates with the centrosome throughout the cell cycle and accumulates on the mitotic centrosome. [provided by RefSeq, Mar 2017]

LRRCC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026181042).

BP6

Variant 8-85109759-G-A is Benign according to our data. Variant chr8-85109759-G-A is described in ClinVar as [Benign]. Clinvar id is 1571909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRCC1	NM_033402.5 linkuse as main transcript	c.269G>A	p.Cys90Tyr	missense_variant	2/19	ENST00000360375.8	NP_208325.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRCC1	ENST00000360375.8 linkuse as main transcript	c.269G>A	p.Cys90Tyr	missense_variant	2/19	1	NM_033402.5	ENSP00000353538	P2	Q9C099-1

Frequencies

GnomAD3 genomes

AF:

0.0757

AC:

11511

AN:

152026

Hom.:

549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0541

Gnomad ASJ

AF:

0.0969

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.0690

GnomAD3 exomes

AF:

0.0908

AC:

21903

AN:

241172

Hom.:

1189

AF XY:

0.0952

AC XY:

12463

AN XY:

130876

show subpopulations

Gnomad AFR exome

AF:

0.0183

Gnomad AMR exome

AF:

0.0420

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.00987

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.114

Gnomad OTH exome

AF:

0.0945

GnomAD4 exome

AF:

0.102

AC:

146647

AN:

1437152

Hom.:

8007

Cov.:

AF XY:

0.104

AC XY:

74097

AN XY:

715342

show subpopulations

Gnomad4 AFR exome

AF:

0.0167

Gnomad4 AMR exome

AF:

0.0440

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.0159

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.0958

GnomAD4 genome

AF:

0.0757

AC:

11518

AN:

152144

Hom.:

549

Cov.:

AF XY:

0.0763

AC XY:

5673

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0217

Gnomad4 AMR

AF:

0.0540

Gnomad4 ASJ

AF:

0.0969

Gnomad4 EAS

AF:

0.0116

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.0716

Alfa

AF:

0.100

Hom.:

847

Bravo

AF:

0.0674

TwinsUK

AF:

0.109

AC:

403

ALSPAC

AF:

0.100

AC:

386

ESP6500AA

AF:

0.0199

AC:

ESP6500EA

AF:

0.110

AC:

898

ExAC

AF:

0.0932

AC:

11254

Asia WGS

AF:

0.0590

AC:

205

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0053

T;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

D;D

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.83

L;.

MutationTaster

Benign

0.55

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.093

Sift

Benign

0.068

T;T

Sift4G

Benign

0.093

T;T

Polyphen

0.91

P;D

Vest4

0.37

MPC

0.31

ClinPred

0.024

GERP RS

5.5

Varity_R

0.18

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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