rs2238116

Positions:

• chr12-6912451-A-G

Variant summary

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

The NM_001135217.2(LRRC23):​c.759-279A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,978 control chromosomes in the GnomAD database, including 12,226 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 0.37 (12226 hom., cov: 31)
• Consequence: LRRC23 NM_001135217.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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 (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC23	NM_001135217.2	c.759-279A>G		intron_variant		ENST00000443597.7	NP_001128689.1
LRRC23	NM_006992.4	c.759-1440A>G		intron_variant			NP_008923.1
LRRC23	NM_201650.3	c.759-279A>G		intron_variant			NP_964013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC23	ENST00000443597.7	c.759-279A>G		intron_variant		1	NM_001135217.2	ENSP00000390932	P1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56504 AN: 151858 Hom.: 12206 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.376

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.372 AC: 56568 AN: 151978 Hom.: 12226 Cov.: 31 AF XY: 0.367 AC XY: 27284 AN XY: 74288

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.378

Alfa AF: 0.313 Hom.: 1653

Bravo AF: 0.384

Asia WGS AF: 0.330 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.56

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: rs2238116; hg19: chr12-7021615;