13-46259582-G-C

Position:

• chr13-46259582-G-C

Variant summary

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

The NM_001282460.2(LRRC63):​c.1227-2327G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,016 control chromosomes in the GnomAD database, including 6,730 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 0.29 (6730 hom., cov: 32)
• Consequence: LRRC63 NM_001282460.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

Genes affected

LRRC63 (HGNC:34296): (leucine rich repeat containing 63) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC63 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC63	NM_001282460.2	c.1227-2327G>C		intron_variant		ENST00000595396.3	NP_001269389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC63	ENST00000595396.3	c.1227-2327G>C		intron_variant		5	NM_001282460.2	ENSP00000469337.1
LRRC63	ENST00000378805.7	n.1227-2327G>C		intron_variant		1		ENSP00000368082.3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44695 AN: 151896 Hom.: 6723 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.294 AC: 44708 AN: 152016 Hom.: 6730 Cov.: 32 AF XY: 0.294 AC XY: 21849 AN XY: 74290

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.298

Alfa AF: 0.292 Hom.: 877

Bravo AF: 0.294

Asia WGS AF: 0.298 AC: 1039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.55

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: rs958546; hg19: chr13-46833717;