11-76659003-T-C

Variant names:

• chr11-76659003-T-C
• rs1320646
• NM_001128922.2:c.*601A>G

Variant summary

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

The NM_001128922.2(LRRC32):​c.*601A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 154,186 control chromosomes in the GnomAD database, including 47,818 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 0.78 (47322 hom., cov: 34)
  • Exomes 𝑓: 0.71 (496 hom.)
• Consequence: LRRC32 NM_001128922.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 12 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)

ENSG00000236304 (HGNC:58233):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC32	NM_001128922.2	c.*601A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000260061.9	NP_001122394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC32	ENST00000260061.9	c.*601A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_001128922.2	ENSP00000260061.5

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119364 AN: 152098 Hom.: 47280 Cov.: 34

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.780

GnomAD4 exome AF: 0.708 AC: 1395 AN: 1970 Hom.: 496 Cov.: 0 AF XY: 0.712 AC XY: 689 AN XY: 968

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AF: 0.659 AC: 232 AN: 352

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AF: 0.705 AC: 86 AN: 122

South Asian (SAS) AF: 0.652 AC: 30 AN: 46

European-Finnish (FIN) AF: 0.740 AC: 77 AN: 104

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.719 AC: 927 AN: 1290

Other (OTH) AF: 0.739 AC: 34 AN: 46

GnomAD4 genome AF: 0.785 AC: 119465 AN: 152216 Hom.: 47322 Cov.: 34 AF XY: 0.783 AC XY: 58248 AN XY: 74426

African (AFR) AF: 0.893 AC: 37091 AN: 41542

American (AMR) AF: 0.709 AC: 10835 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2566 AN: 3470

East Asian (EAS) AF: 0.896 AC: 4635 AN: 5174

South Asian (SAS) AF: 0.752 AC: 3629 AN: 4828

European-Finnish (FIN) AF: 0.744 AC: 7886 AN: 10602

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50267 AN: 67994

Other (OTH) AF: 0.779 AC: 1643 AN: 2110

Alfa AF: 0.745 Hom.: 76628

Bravo AF: 0.788

Asia WGS AF: 0.822 AC: 2859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.66
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1320646; hg19: chr11-76370047;