Genetic Variant LRRC32:c.*1626C>T (chr11-76657978-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001128922.2(LRRC32):c.*1626C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 152,464 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 19 hom., cov: 33)

Exomes 𝑓: 0.0063 ( 0 hom. )

Consequence

LRRC32
NM_001128922.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.35

Publications

1 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:

LRRC32-AS1 (HGNC:58233):

LRRC32-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 11-76657978-G-A is Benign according to our data. Variant chr11-76657978-G-A is described in ClinVar as Benign. ClinVar VariationId is 1879212.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

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	UniProt
LRRC32	NM_001128922.2	MANE Select	c.*1626C>T	3_prime_UTR	Exon 3 of 3	NP_001122394.1	Q14392
LRRC32	NM_001370187.1		c.*78C>T	3_prime_UTR	Exon 4 of 4	NP_001357116.1	Q14392
LRRC32	NM_001370188.1		c.*78C>T	3_prime_UTR	Exon 4 of 4	NP_001357117.1	Q14392

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LRRC32	ENST00000260061.9	TSL:1 MANE Select	c.*1626C>T	3_prime_UTR	Exon 3 of 3	ENSP00000260061.5	Q14392
LRRC32	ENST00000407242.6	TSL:1	c.*1626C>T	3_prime_UTR	Exon 3 of 3	ENSP00000384126.2	Q14392
LRRC32-AS1	ENST00000447519.2	TSL:1	n.173+822G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1595

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.00641

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.0210

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0150

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.00633

AC:

AN:

158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00725

AC:

AN:

138

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0105

AC:

1595

AN:

152306

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

781

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00229

AC:

AN:

41556

American (AMR)

AF:

0.00641

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.00704

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0210

AC:

223

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0150

AC:

1019

AN:

68028

Other (OTH)

AF:

0.0109

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

166

249

332

415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0132

Hom.:

Bravo

AF:

0.00965

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.1

(source)

DANN

Benign

0.68

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism

(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