8-85109697-T-A

Position:

• chr8-85109697-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000360375.8(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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.040 (148 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1479 hom.)
• Consequence: LRRCC1 ENST00000360375.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.32

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]

ACMG classification

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	c.207T>A	p.His69Gln	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	c.207T>A	p.His69Gln	missense_variant	2/19	1	NM_033402.5	ENSP00000353538	P2

Frequencies

GnomAD3 genomes AF: 0.0402 AC: 6118 AN: 152138 Hom.: 148 Cov.: 33

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

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.: 27 AF XY: 0.0420 AC XY: 30316 AN XY: 722190

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.: 33 AF XY: 0.0378 AC XY: 2811 AN XY: 74452

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: 60 AN: 3474

EpiCase AF: 0.0448

EpiControl AF: 0.0436

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	T;D
MetaRNN	Benign	0.0088	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.15	N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.61	T
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	T
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

Other links and lift over

dbSNP: rs16913589; hg19: chr8-86021932;