rs9349688

chr6-53897294-A-Gchr6-53897294-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018214.5(LRRC1):c.577A>G(p.Ile193Val) variant causes a missense change. The variant allele was found at a frequency of 0.093 in 1,607,402 control chromosomes in the GnomAD database, including 9,135 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.089 (913 hom., cov: 32)
  • Exomes 𝑓: 0.093 (8222 hom.)
• Consequence: LRRC1 NM_018214.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53

Genes affected

LRRC1 (HGNC:14307): (leucine rich repeat containing 1) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013781786).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC1	NM_018214.5	c.577A>G	p.Ile193Val	missense_variant	7/14	ENST00000370888.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC1	ENST00000370888.6	c.577A>G	p.Ile193Val	missense_variant	7/14	1	NM_018214.5	P1
LRRC1	ENST00000487251.5	c.573A>G	p.Gln191=	synonymous_variant, NMD_transcript_variant	8/11	2

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13480 AN: 152090 Hom.: 905 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.0769

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.104

GnomAD3 exomes AF: 0.120 AC: 29943 AN: 249814 Hom.: 2647 AF XY: 0.113 AC XY: 15279 AN XY: 135090

Gnomad AFR exome AF: 0.0217

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.244

Gnomad SAS exome AF: 0.0704

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0841

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.0935 AC: 136029 AN: 1455194 Hom.: 8222 Cov.: 29 AF XY: 0.0932 AC XY: 67504 AN XY: 724270

Gnomad4 AFR exome AF: 0.0197

Gnomad4 AMR exome AF: 0.262

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.257

Gnomad4 SAS exome AF: 0.0686

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.0836

Gnomad4 OTH exome AF: 0.0969

GnomAD4 genome AF: 0.0888 AC: 13509 AN: 152208 Hom.: 913 Cov.: 32 AF XY: 0.0923 AC XY: 6869 AN XY: 74404

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.0772

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0879

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0913 Hom.: 1631

Bravo AF: 0.0958

TwinsUK AF: 0.0868 AC: 322

ALSPAC AF: 0.0784 AC: 302

ESP6500AA AF: 0.0254 AC: 112

ESP6500EA AF: 0.0921 AC: 792

ExAC AF: 0.110 AC: 13327

Asia WGS AF: 0.145 AC: 504 AN: 3478

EpiCase AF: 0.0972

EpiControl AF: 0.0939

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.041
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	0.0000024	P
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.085
Sift	Benign	0.077	T
Sift4G	Benign	0.15	T
Polyphen		0.45	B
Vest4		0.071
MPC		0.88
ClinPred		0.023	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.27

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: rs9349688; hg19: chr6-53762092; COSMIC: COSV63829157;