12-6913959-A-G

Variant summary

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

The ENST00000323702.9(LRRC23):c.827A>G(p.Glu276Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,613,016 control chromosomes in the GnomAD database, including 87,982 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 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 0.41 (15834 hom., cov: 30)
  • Exomes 𝑓: 0.30 (72148 hom.)
• Consequence: LRRC23 ENST00000323702.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910

Genes affected

LRRC23 (HGNC:19138): (leucine rich repeat containing 23) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENO2 (HGNC:3353): (enolase 2) This gene encodes one of the three enolase isoenzymes found in mammals. This isoenzyme, a homodimer, is found in mature neurons and cells of neuronal origin. A switch from alpha enolase to gamma enolase occurs in neural tissue during development in rats and primates. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6284145E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC23	NM_001135217.2	c.*93A>G		3_prime_UTR_variant	8/8	ENST00000443597.7
LRRC23	NM_006992.4	c.827A>G	p.Glu276Gly	missense_variant	7/7
LRRC23	NM_201650.3	c.*93A>G		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC23	ENST00000443597.7	c.*93A>G		3_prime_UTR_variant	8/8	1	NM_001135217.2	P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62720 AN: 151840 Hom.: 15799 Cov.: 30

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.411

GnomAD3 exomes AF: 0.324 AC: 81339 AN: 250882 Hom.: 15346 AF XY: 0.321 AC XY: 43587 AN XY: 135624

Gnomad AFR exome AF: 0.736

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.290

Gnomad EAS exome AF: 0.461

Gnomad SAS exome AF: 0.343

Gnomad FIN exome AF: 0.237

Gnomad NFE exome AF: 0.288

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.302 AC: 441821 AN: 1461058 Hom.: 72148 Cov.: 34 AF XY: 0.303 AC XY: 220426 AN XY: 726890

Gnomad4 AFR exome AF: 0.749

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.345

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.332

GnomAD4 genome AF: 0.413 AC: 62803 AN: 151958 Hom.: 15834 Cov.: 30 AF XY: 0.408 AC XY: 30315 AN XY: 74276

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.414

Alfa AF: 0.315 Hom.: 19295

Bravo AF: 0.431

TwinsUK AF: 0.267 AC: 990

ALSPAC AF: 0.268 AC: 1032

ESP6500AA AF: 0.707 AC: 3115

ESP6500EA AF: 0.284 AC: 2441

ExAC AF: 0.333 AC: 40422

Asia WGS AF: 0.406 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	5.5
Dann	Benign	0.94
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0000016	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.062
Sift	Benign	0.12	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.051
ClinPred		0.00048	T
GERP RS		-0.78

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: rs710415; hg19: chr12-7023123; COSMIC: COSV50386845; COSMIC: COSV50386845;