rs10500541

Variant names:

• chr16-67358124-A-G
• rs10500541
• NM_018296.6:c.578-5466A>G

Variant summary

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

The NM_018296.6(LRRC36):​c.578-5466A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 151,644 control chromosomes in the GnomAD database, including 130 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 0.032 (130 hom., cov: 31)
• Consequence: LRRC36 NM_018296.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 7 publications found

Genes affected

LRRC36 (HGNC:25615): (leucine rich repeat containing 36)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC36	NM_018296.6	c.578-5466A>G		intron_variant	Intron 5 of 13	ENST00000329956.11	NP_060766.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC36	ENST00000329956.11	c.578-5466A>G		intron_variant	Intron 5 of 13	1	NM_018296.6	ENSP00000329943.6

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4857 AN: 151528 Hom.: 130 Cov.: 31

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000777

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0182

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

GnomAD4 genome AF: 0.0321 AC: 4868 AN: 151644 Hom.: 130 Cov.: 31 AF XY: 0.0357 AC XY: 2642 AN XY: 74056

African (AFR) AF: 0.0267 AC: 1102 AN: 41342

American (AMR) AF: 0.0139 AC: 212 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.000779 AC: 4 AN: 5136

South Asian (SAS) AF: 0.0690 AC: 332 AN: 4810

European-Finnish (FIN) AF: 0.106 AC: 1099 AN: 10406

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0302 AC: 2050 AN: 67950

Other (OTH) AF: 0.0180 AC: 38 AN: 2108

Alfa AF: 0.0260 Hom.: 69

Bravo AF: 0.0241

Asia WGS AF: 0.0470 AC: 162 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism

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: rs10500541; hg19: chr16-67392027;