Variant chr8-85109697-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_033402.5(LRRCC1):c.207T>A(p.His69Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 1,602,330 control chromosomes in the GnomAD database, including 1,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.040 ( 148 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1479 hom. )

Consequence

LRRCC1
NM_033402.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.32

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0087578).

BP6

Variant 8-85109697-T-A is Benign according to our data. Variant chr8-85109697-T-A is described in ClinVar as [Benign]. Clinvar id is 1597582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0402 (6125/152256) while in subpopulation NFE AF= 0.0498 (3385/68010). AF 95% confidence interval is 0.0484. There are 148 homozygotes in gnomad4. There are 2811 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 148 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRCC1	NM_033402.5 link	c.207T>A	p.His69Gln	missense_variant	2/19	ENST00000360375.8	NP_208325.3	Q9C099-1B4DTJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRCC1	ENST00000360375.8 link	c.207T>A	p.His69Gln	missense_variant	2/19	1	NM_033402.5	ENSP00000353538.3		Q9C099-1

Frequencies

GnomAD3 genomes

AF:

0.0402

AC:

6118

AN:

152138

Hom.:

148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0448

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0275

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0498

Gnomad OTH

AF:

0.0406

GnomAD3 exomes

AF:

0.0319

AC:

7922

AN:

248694

Hom.:

152

AF XY:

0.0319

AC XY:

4300

AN XY:

134958

show subpopulations

Gnomad AFR exome

AF:

0.0433

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0213

Gnomad EAS exome

AF:

0.00128

Gnomad SAS exome

AF:

0.0131

Gnomad FIN exome

AF:

0.0243

Gnomad NFE exome

AF:

0.0462

Gnomad OTH exome

AF:

0.0333

GnomAD4 exome

AF:

0.0429

AC:

62171

AN:

1450074

Hom.:

1479

Cov.:

AF XY:

0.0420

AC XY:

30316

AN XY:

722190

show subpopulations

Gnomad4 AFR exome

AF:

0.0497

Gnomad4 AMR exome

AF:

0.0209

Gnomad4 ASJ exome

AF:

0.0212

Gnomad4 EAS exome

AF:

0.000329

Gnomad4 SAS exome

AF:

0.0131

Gnomad4 FIN exome

AF:

0.0262

Gnomad4 NFE exome

AF:

0.0492

Gnomad4 OTH exome

AF:

0.0370

GnomAD4 genome

AF:

0.0402

AC:

6125

AN:

152256

Hom.:

148

Cov.:

AF XY:

0.0378

AC XY:

2811

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0448

Gnomad4 AMR

AF:

0.0274

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.0218

Gnomad4 NFE

AF:

0.0498

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0443

Hom.:

120

Bravo

AF:

0.0408

TwinsUK

AF:

0.0534

AC:

198

ALSPAC

AF:

0.0402

AC:

155

ESP6500AA

AF:

0.0353

AC:

130

ESP6500EA

AF:

0.0454

AC:

371

ExAC

AF:

0.0316

AC:

3814

Asia WGS

AF:

0.0170

AC:

AN:

3474

EpiCase

AF:

0.0448

EpiControl

AF:

0.0436

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 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

T;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.80

T;D

MetaRNN

Benign

0.0088

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.15

N;.

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Benign

0.10

Sift

Uncertain

0.0040

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.51

MutPred

0.14

Gain of disorder (P = 0.2358);.;

MPC

0.25

ClinPred

0.033

GERP RS

3.4

Varity_R

0.50

gMVP

0.58

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