11-76669313-C-T

Variant names:

• chr11-76669313-C-T
• rs10899249
• NM_001128922.2:c.-5+1301G>A

Variant summary

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

The NM_001128922.2(LRRC32):​c.-5+1301G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,056 control chromosomes in the GnomAD database, including 20,470 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 0.52 (20470 hom., cov: 29)
• Consequence: LRRC32 NM_001128922.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 8 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC32	NM_001128922.2	c.-5+1301G>A		intron_variant	Intron 1 of 2	ENST00000260061.9	NP_001122394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC32	ENST00000260061.9	c.-5+1301G>A		intron_variant	Intron 1 of 2	1	NM_001128922.2	ENSP00000260061.5
LRRC32	ENST00000407242.6	c.-5+449G>A		intron_variant	Intron 1 of 2	1		ENSP00000384126.2
LRRC32	ENST00000421973.1	c.-5+449G>A		intron_variant	Intron 1 of 2	1		ENSP00000413331.1
LRRC32	ENST00000404995.5	c.-5+1301G>A		intron_variant	Intron 1 of 3	5		ENSP00000385766.1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78283 AN: 150940 Hom.: 20458 Cov.: 29

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.519 AC: 78338 AN: 151056 Hom.: 20470 Cov.: 29 AF XY: 0.517 AC XY: 38093 AN XY: 73744

African (AFR) AF: 0.541 AC: 22160 AN: 40960

American (AMR) AF: 0.548 AC: 8349 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2080 AN: 3470

East Asian (EAS) AF: 0.510 AC: 2606 AN: 5108

South Asian (SAS) AF: 0.486 AC: 2312 AN: 4754

European-Finnish (FIN) AF: 0.417 AC: 4334 AN: 10386

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34734 AN: 67844

Other (OTH) AF: 0.554 AC: 1162 AN: 2098

Alfa AF: 0.519 Hom.: 64020

Bravo AF: 0.531

Asia WGS AF: 0.540 AC: 1881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.76
PhyloP100		-0.55
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: rs10899249; hg19: chr11-76380357;