12-122194060-T-C

Variant names:

• chr12-122194060-T-C
• rs11060333
• NM_001098519.2:c.1349+1056T>C

Variant summary

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

The NM_001098519.2(LRRC43):​c.1349+1056T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,156 control chromosomes in the GnomAD database, including 5,118 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 0.22 (5118 hom., cov: 31)
• Consequence: LRRC43 NM_001098519.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 8 publications found

Genes affected

LRRC43 (HGNC:28562): (leucine rich repeat containing 43)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC43	NM_001098519.2	c.1349+1056T>C		intron_variant	Intron 7 of 11	ENST00000339777.5	NP_001091989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC43	ENST00000339777.5	c.1349+1056T>C		intron_variant	Intron 7 of 11	5	NM_001098519.2	ENSP00000344233.4
LRRC43	ENST00000541498.5	n.431-6472T>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33862 AN: 152038 Hom.: 5122 Cov.: 31

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.223 AC: 33860 AN: 152156 Hom.: 5118 Cov.: 31 AF XY: 0.231 AC XY: 17214 AN XY: 74368

African (AFR) AF: 0.0653 AC: 2715 AN: 41556

American (AMR) AF: 0.190 AC: 2898 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 786 AN: 3472

East Asian (EAS) AF: 0.709 AC: 3665 AN: 5168

South Asian (SAS) AF: 0.318 AC: 1533 AN: 4814

European-Finnish (FIN) AF: 0.346 AC: 3652 AN: 10556

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17936 AN: 67986

Other (OTH) AF: 0.211 AC: 445 AN: 2110

Alfa AF: 0.244 Hom.: 9561

Bravo AF: 0.205

Asia WGS AF: 0.428 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.81
PhyloP100		0.27
Mutation Taster		=100/0	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: rs11060333; hg19: chr12-122678607;