rs3740778

Positions:

• chr11-76661374-T-C
• chr11-76661374-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001128922.2(LRRC32):​c.219A>G​(p.Thr73Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 1,614,068 control chromosomes in the GnomAD database, including 616,823 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 0.89 (60123 hom., cov: 32)
  • Exomes 𝑓: 0.87 (556700 hom.)
• Consequence: LRRC32 NM_001128922.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

Genes affected

LRRC32 (HGNC:4161): (leucine rich repeat containing 32) This gene encodes a type I membrane protein which contains 20 leucine-rich repeats. Alterations in the chromosomal region 11q13-11q14 are involved in several pathologies. [provided by RefSeq, Jul 2008]

ENSG00000236304 (HGNC:58233):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC32	NM_001128922.2	c.219A>G	p.Thr73Thr	synonymous_variant	3/3	ENST00000260061.9	NP_001122394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC32	ENST00000260061.9	c.219A>G	p.Thr73Thr	synonymous_variant	3/3	1	NM_001128922.2	ENSP00000260061.5

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134823 AN: 152112 Hom.: 60068 Cov.: 32

Gnomad AFR AF: 0.974

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.889

GnomAD3 exomes AF: 0.863 AC: 216883 AN: 251286 Hom.: 94021 AF XY: 0.867 AC XY: 117807 AN XY: 135806

Gnomad AFR exome AF: 0.974

Gnomad AMR exome AF: 0.799

Gnomad ASJ exome AF: 0.905

Gnomad EAS exome AF: 0.792

Gnomad SAS exome AF: 0.916

Gnomad FIN exome AF: 0.805

Gnomad NFE exome AF: 0.871

Gnomad OTH exome AF: 0.869

GnomAD4 exome AF: 0.872 AC: 1274186 AN: 1461838 Hom.: 556700 Cov.: 61 AF XY: 0.873 AC XY: 635010 AN XY: 727218

Gnomad4 AFR exome AF: 0.978

Gnomad4 AMR exome AF: 0.801

Gnomad4 ASJ exome AF: 0.902

Gnomad4 EAS exome AF: 0.715

Gnomad4 SAS exome AF: 0.917

Gnomad4 FIN exome AF: 0.804

Gnomad4 NFE exome AF: 0.875

Gnomad4 OTH exome AF: 0.881

GnomAD4 genome AF: 0.886 AC: 134934 AN: 152230 Hom.: 60123 Cov.: 32 AF XY: 0.884 AC XY: 65798 AN XY: 74438

Gnomad4 AFR AF: 0.974

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.900

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.890

Alfa AF: 0.877 Hom.: 93529

Bravo AF: 0.892

Asia WGS AF: 0.868 AC: 3020 AN: 3478

EpiCase AF: 0.875

EpiControl AF: 0.882

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.31
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: rs3740778; hg19: chr11-76372418; COSMIC: COSV52633164; COSMIC: COSV52633164;