NM_001128922.2:c.-4-817C>T

Variant names:

• chr11-76666775-G-A
• rs6592657
• NM_001128922.2:c.-4-817C>T

Variant summary

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

The NM_001128922.2(LRRC32):​c.-4-817C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,212 control chromosomes in the GnomAD database, including 11,632 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 0.38 (11632 hom., cov: 34)
• Consequence: LRRC32 NM_001128922.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• Publications: 10 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC32	NM_001128922.2	c.-4-817C>T		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.-4-817C>T		intron_variant	Intron 1 of 2	1	NM_001128922.2	ENSP00000260061.5
LRRC32	ENST00000407242.6	c.-4-817C>T		intron_variant	Intron 1 of 2	1		ENSP00000384126.2
LRRC32	ENST00000421973.1	c.-4-817C>T		intron_variant	Intron 1 of 2	1		ENSP00000413331.1
LRRC32	ENST00000404995.5	c.-4-817C>T		intron_variant	Intron 1 of 3	5		ENSP00000385766.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58030 AN: 152094 Hom.: 11626 Cov.: 34

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.381 AC: 58049 AN: 152212 Hom.: 11632 Cov.: 34 AF XY: 0.382 AC XY: 28461 AN XY: 74430

African (AFR) AF: 0.258 AC: 10702 AN: 41530

American (AMR) AF: 0.444 AC: 6793 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1809 AN: 3472

East Asian (EAS) AF: 0.250 AC: 1292 AN: 5178

South Asian (SAS) AF: 0.462 AC: 2228 AN: 4822

European-Finnish (FIN) AF: 0.357 AC: 3788 AN: 10606

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29974 AN: 67988

Other (OTH) AF: 0.423 AC: 893 AN: 2110

Alfa AF: 0.428 Hom.: 24637

Bravo AF: 0.380

Asia WGS AF: 0.390 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.68
PhyloP100		0.11
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: rs6592657; hg19: chr11-76377819;