rs1057077

Positions:

• chr12-6912921-T-A

Variant summary

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

The NM_001135217.2(LRRC23):​c.950T>A​(p.Val317Glu) variant causes a missense change. The variant allele was found at a frequency of 0.298 in 1,613,650 control chromosomes in the GnomAD database, including 77,324 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.38 (12452 hom., cov: 31)
  • Exomes 𝑓: 0.29 (64872 hom.)
• Consequence: LRRC23 NM_001135217.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70

Genes affected

LRRC23 (HGNC:19138): (leucine rich repeat containing 23) Predicted to be active 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=2.2957329E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC23	NM_001135217.2	c.950T>A	p.Val317Glu	missense_variant	7/8	ENST00000443597.7
LRRC23	NM_201650.3	c.950T>A	p.Val317Glu	missense_variant	7/8
LRRC23	NM_006992.4	c.759-970T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC23	ENST00000443597.7	c.950T>A	p.Val317Glu	missense_variant	7/8	1	NM_001135217.2	P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56942 AN: 151692 Hom.: 12430 Cov.: 31

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.379

GnomAD3 exomes AF: 0.297 AC: 74574 AN: 251474 Hom.: 12452 AF XY: 0.297 AC XY: 40407 AN XY: 135914

Gnomad AFR exome AF: 0.636

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.237

Gnomad SAS exome AF: 0.331

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.293

GnomAD4 exome AF: 0.290 AC: 424413 AN: 1461840 Hom.: 64872 Cov.: 38 AF XY: 0.292 AC XY: 212169 AN XY: 727226

Gnomad4 AFR exome AF: 0.644

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome AF: 0.376 AC: 57011 AN: 151810 Hom.: 12452 Cov.: 31 AF XY: 0.370 AC XY: 27483 AN XY: 74194

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.381

Alfa AF: 0.309 Hom.: 2624

Bravo AF: 0.387

TwinsUK AF: 0.264 AC: 979

ALSPAC AF: 0.265 AC: 1022

ESP6500AA AF: 0.617 AC: 2718

ESP6500EA AF: 0.280 AC: 2410

ExAC AF: 0.304 AC: 36970

Asia WGS AF: 0.334 AC: 1160 AN: 3478

EpiCase AF: 0.293

EpiControl AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.62
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.0069	N
MetaRNN	Benign	0.000023	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.73	N;N
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.47	T
PROVEAN	Benign	2.9	N;N
REVEL	Benign	0.14
Sift	Benign	0.53	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.048
MPC		0.23
ClinPred		0.0041	T
GERP RS		5.3
Varity_R		0.11
gMVP		0.14

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: rs1057077; hg19: chr12-7022085; COSMIC: COSV50387059; COSMIC: COSV50387059;