NM_018214.5:c.577A>G

Variant names:

• chr6-53897294-A-G
• rs9349688
• NM_018214.5:c.577A>G

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 28 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018214.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC1	NM_018214.5	MANE Select	c.577A>G	p.Ile193Val	missense	Exon 7 of 14	NP_060684.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC1	ENST00000370888.6	TSL:1 MANE Select	c.577A>G	p.Ile193Val	missense	Exon 7 of 14	ENSP00000359925.1
	LRRC1	ENST00000487251.5	TSL:2	n.573A>G		non_coding_transcript_exon	Exon 8 of 11	ENSP00000435217.1

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

GnomAD2 exomes AF: 0.120 AC: 29943 AN: 249814 AF XY: 0.113

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 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

African (AFR) AF: 0.0197 AC: 657 AN: 33418

American (AMR) AF: 0.262 AC: 11669 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3305 AN: 26064

East Asian (EAS) AF: 0.257 AC: 10188 AN: 39600

South Asian (SAS) AF: 0.0686 AC: 5899 AN: 85978

European-Finnish (FIN) AF: 0.104 AC: 5474 AN: 52770

Middle Eastern (MID) AF: 0.0799 AC: 454 AN: 5684

European-Non Finnish (NFE) AF: 0.0836 AC: 92553 AN: 1106930

Other (OTH) AF: 0.0969 AC: 5830 AN: 60180

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

African (AFR) AF: 0.0244 AC: 1014 AN: 41550

American (AMR) AF: 0.201 AC: 3079 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3468

East Asian (EAS) AF: 0.245 AC: 1266 AN: 5166

South Asian (SAS) AF: 0.0772 AC: 372 AN: 4818

European-Finnish (FIN) AF: 0.104 AC: 1105 AN: 10586

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0879 AC: 5975 AN: 68006

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.0905 Hom.: 2321

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 v4.9

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
PhyloP100		4.5
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
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

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