Genetic Variant NM_001128922.2:c.*863A>C (chr11-76658741-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001128922.2(LRRC32):c.*863A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,706 control chromosomes in the GnomAD database, including 8,697 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 0.33 ( 8652 hom., cov: 33)

Exomes 𝑓: 0.39 ( 45 hom. )

Consequence

LRRC32
NM_001128922.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.193

Publications

12 publications found

Variant links:

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 links:

ENSG00000236304 (HGNC:58233):

ENSG00000236304 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.348 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LRRC32	NM_001128922.2	MANE Select	c.*863A>C	3_prime_UTR	Exon 3 of 3	NP_001122394.1
LRRC32	NR_163259.1		n.3033A>C	non_coding_transcript_exon	Exon 3 of 4
LRRC32	NM_005512.3		c.*863A>C	3_prime_UTR	Exon 3 of 3	NP_005503.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LRRC32	ENST00000260061.9	TSL:1 MANE Select	c.*863A>C	3_prime_UTR	Exon 3 of 3	ENSP00000260061.5
LRRC32	ENST00000407242.6	TSL:1	c.*863A>C	3_prime_UTR	Exon 3 of 3	ENSP00000384126.2
ENSG00000236304	ENST00000447519.2	TSL:1	n.174-867T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.335

AC:

50904

AN:

151996

Hom.:

8656

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.353

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.320

GnomAD4 exome

AF:

0.387

AC:

230

AN:

594

Hom.:

Cov.:

AF XY:

0.392

AC XY:

146

AN XY:

372

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.291

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.408

AC:

183

AN:

448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.354

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.335

AC:

50910

AN:

152112

Hom.:

8652

Cov.:

AF XY:

0.335

AC XY:

24896

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.294

AC:

12194

AN:

41486

American (AMR)

AF:

0.356

AC:

5439

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

917

AN:

3472

East Asian (EAS)

AF:

0.353

AC:

1829

AN:

5174

South Asian (SAS)

AF:

0.349

AC:

1686

AN:

4826

European-Finnish (FIN)

AF:

0.385

AC:

4066

AN:

10570

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.348

AC:

23668

AN:

67974

Other (OTH)

AF:

0.319

AC:

676

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1800

3600

5401

7201

9001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.337

Hom.:

11230

Bravo

AF:

0.330

Asia WGS

AF:

0.326

AC:

1132

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.3

(source)

DANN

Benign

0.77

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over