12-6913959-A-G

Variant names:

• chr12-6913959-A-G
• rs710415
• ENST00000323702.9:c.827A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000443597.7(LRRC23):​c.*93A>G variant causes a 3 prime UTR 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. 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 ENST00000443597.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 48 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443597.7. 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
	LRRC23	NM_001135217.2	MANE Select	c.*93A>G		3_prime_UTR	Exon 8 of 8	NP_001128689.1
	LRRC23	NM_006992.4		c.827A>G	p.Glu276Gly	missense	Exon 7 of 7	NP_008923.1
	LRRC23	NM_201650.3		c.*93A>G		3_prime_UTR	Exon 8 of 8	NP_964013.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC23	ENST00000323702.9	TSL:1	c.827A>G	p.Glu276Gly	missense	Exon 7 of 7	ENSP00000317464.5
	LRRC23	ENST00000429740.1	TSL:1	c.559A>G	p.Asn187Asp	missense	Exon 4 of 4	ENSP00000397192.1
	LRRC23	ENST00000443597.7	TSL:1 MANE Select	c.*93A>G		3_prime_UTR	Exon 8 of 8	ENSP00000390932.2

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

GnomAD2 exomes AF: 0.324 AC: 81339 AN: 250882 AF XY: 0.321

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 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

African (AFR) AF: 0.749 AC: 25056 AN: 33440

American (AMR) AF: 0.239 AC: 10672 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7518 AN: 26106

East Asian (EAS) AF: 0.461 AC: 18302 AN: 39666

South Asian (SAS) AF: 0.345 AC: 29751 AN: 86178

European-Finnish (FIN) AF: 0.237 AC: 12650 AN: 53396

Middle Eastern (MID) AF: 0.451 AC: 2596 AN: 5758

European-Non Finnish (NFE) AF: 0.284 AC: 315222 AN: 1111508

Other (OTH) AF: 0.332 AC: 20054 AN: 60346

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

African (AFR) AF: 0.722 AC: 29911 AN: 41428

American (AMR) AF: 0.317 AC: 4837 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3468

East Asian (EAS) AF: 0.457 AC: 2351 AN: 5144

South Asian (SAS) AF: 0.338 AC: 1629 AN: 4816

European-Finnish (FIN) AF: 0.231 AC: 2439 AN: 10568

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19362 AN: 67942

Other (OTH) AF: 0.414 AC: 872 AN: 2108

Alfa AF: 0.335 Hom.: 36088

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
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
PhyloP100		-0.091
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
PromoterAI		-0.016	Neutral
Mutation Taster		=99/1	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: rs710415; hg19: chr12-7023123; COSMIC: COSV50386845; COSMIC: COSV50386845;