Variant 17-32021245-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000341671.12(LRRC37B):c.99C>A(p.Asp33Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LRRC37B
ENST00000341671.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Variant links:

Genes affected

LRRC37B (HGNC:29070): (leucine rich repeat containing 37B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14002591).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC37B	NM_001321350.2 linkuse as main transcript	c.1-148C>A		intron_variant		ENST00000543378.7
LRRC37B	NM_052888.3 linkuse as main transcript	c.99C>A	p.Asp33Glu	missense_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC37B	ENST00000543378.7 linkuse as main transcript	c.1-148C>A		intron_variant		2	NM_001321350.2	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251348

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460392

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726498

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.99C>A (p.D33E) alteration is located in exon 1 (coding exon 1) of the LRRC37B gene. This alteration results from a C to A substitution at nucleotide position 99, causing the aspartic acid (D) at amino acid position 33 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.43

CADD

Benign

2.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

.;T;T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.68

T;T;T;.

M_CAP

Benign

0.012

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.6

.;.;M;M

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.5

N;.;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0030

D;.;D;D

Sift4G

Benign

0.33

T;T;T;T

Polyphen

0.98

.;.;D;D

Vest4

0.038

MutPred

0.32

.;.;Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.22

MPC

0.28

ClinPred

0.39

GERP RS

1.9

Varity_R

0.086

gMVP

0.034

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over