11-76661374-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001128922.2(LRRC32):​c.219A>C​(p.Thr73Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-2 with no splicing effect.

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>C	p.Thr73Thr	synonymous	Exon 3 of 3	NP_001122394.1	Q14392
	LRRC32	NM_001370187.1		c.219A>C	p.Thr73Thr	synonymous	Exon 3 of 4	NP_001357116.1	Q14392
	LRRC32	NM_001370188.1		c.219A>C	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>C	p.Thr73Thr	synonymous	Exon 3 of 3	ENSP00000260061.5	Q14392
	LRRC32	ENST00000407242.6	TSL:1	c.219A>C	p.Thr73Thr	synonymous	Exon 3 of 3	ENSP00000384126.2	Q14392
	LRRC32	ENST00000421973.1	TSL:1	c.219A>C	p.Thr73Thr	synonymous	Exon 3 of 3	ENSP00000413331.1	C9JYU3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.60
PhyloP100		-2.0

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;