11-76661374-T-C

Variant names:

• chr11-76661374-T-C
• rs3740778
• NM_001128922.2:c.219A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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]

LRRC32 Gene-Disease associations (from GenCC):

• cleft palate, proliferative retinopathy, and developmental delay

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

LRRC32-AS1 (HGNC:58233):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128922.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC32	NM_001128922.2	MANE Select	c.219A>G	p.Thr73Thr	synonymous	Exon 3 of 3	NP_001122394.1	Q14392
	LRRC32	NM_001370187.1		c.219A>G	p.Thr73Thr	synonymous	Exon 3 of 4	NP_001357116.1	Q14392
	LRRC32	NM_001370188.1		c.219A>G	p.Thr73Thr	synonymous	Exon 3 of 4	NP_001357117.1	Q14392

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC32	ENST00000260061.9	TSL:1 MANE Select	c.219A>G	p.Thr73Thr	synonymous	Exon 3 of 3	ENSP00000260061.5	Q14392
	LRRC32	ENST00000407242.6	TSL:1	c.219A>G	p.Thr73Thr	synonymous	Exon 3 of 3	ENSP00000384126.2	Q14392
	LRRC32	ENST00000421973.1	TSL:1	c.219A>G	p.Thr73Thr	synonymous	Exon 3 of 3	ENSP00000413331.1	C9JYU3

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

GnomAD2 exomes AF: 0.863 AC: 216883 AN: 251286 AF XY: 0.867

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 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

African (AFR) AF: 0.978 AC: 32751 AN: 33480

American (AMR) AF: 0.801 AC: 35810 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 23578 AN: 26136

East Asian (EAS) AF: 0.715 AC: 28389 AN: 39700

South Asian (SAS) AF: 0.917 AC: 79077 AN: 86254

European-Finnish (FIN) AF: 0.804 AC: 42932 AN: 53416

Middle Eastern (MID) AF: 0.940 AC: 5422 AN: 5766

European-Non Finnish (NFE) AF: 0.875 AC: 972994 AN: 1111980

Other (OTH) AF: 0.881 AC: 53233 AN: 60396

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

African (AFR) AF: 0.974 AC: 40458 AN: 41556

American (AMR) AF: 0.823 AC: 12592 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3124 AN: 3470

East Asian (EAS) AF: 0.789 AC: 4069 AN: 5160

South Asian (SAS) AF: 0.911 AC: 4397 AN: 4826

European-Finnish (FIN) AF: 0.810 AC: 8586 AN: 10600

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58672 AN: 68004

Other (OTH) AF: 0.890 AC: 1879 AN: 2112

Alfa AF: 0.878 Hom.: 123844

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.31
DANN	Benign	0.56
PhyloP100		-2.0
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: rs3740778; hg19: chr11-76372418; COSMIC: COSV52633164; COSMIC: COSV52633164;