Genetic Variant LBHD1:p.Gln187Arg (chr11-62664952-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024099.5(LBHD1):c.560A>G(p.Gln187Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LBHD1
NM_024099.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

Publications

0 publications found

Variant links:

Genes affected

LBHD1 (HGNC:28351): (LBH domain containing 1) This gene shares three exons in common with another gene, chromosome 11 open reading frame 98 (GeneID:102288414), but the encoded protein uses a reading frame that is different from that of the chromosome 11 open reading frame 98 gene. [provided by RefSeq, Nov 2017]

LBHD1 links:

C11orf98 (HGNC:51238): (chromosome 11 open reading frame 98) This gene shares three exons in common with another gene, LBH domain containing 1 (GeneID:79081), but the encoded protein uses a reading frame that is different from that of the LBH domain containing 1 gene. [provided by RefSeq, Nov 2017]

C11orf98 links:

ENSG00000255432 (HGNC:):

ENSG00000255432 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBHD1	NM_024099.5 link	c.560A>G	p.Gln187Arg	missense_variant	Exon 5 of 7	ENST00000354588.8	NP_077004.2	Q9BQE6-2A0A024R584
C11orf98	NM_001286086.2 link	c.61A>G	p.Lys21Glu	missense_variant	Exon 2 of 4	ENST00000524958.6	NP_001273015.1	E9PRG8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LBHD1	ENST00000354588.8 link	c.560A>G	p.Gln187Arg	missense_variant	Exon 5 of 7	1	NM_024099.5	ENSP00000346600.3	Q9BQE6-2
C11orf98	ENST00000524958.6 link	c.61A>G	p.Lys21Glu	missense_variant	Exon 2 of 4	2	NM_001286086.2	ENSP00000432523.2	E9PRG8
ENSG00000255432	ENST00000528405.1 link	c.61A>G	p.Lys21Glu	missense_variant	Exon 2 of 4	4		ENSP00000435188.1	E9PLD3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459818

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726090

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

85954

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111492

Other (OTH)

AF:

0.00

AC:

AN:

60308

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

Dec 05, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.560A>G (p.Q187R) alteration is located in exon 5 (coding exon 4) of the LBHD1 gene. This alteration results from a A to G substitution at nucleotide position 560, causing the glutamine (Q) at amino acid position 187 to be replaced by an arginine (R). 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

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.46

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;.;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

D;D;T

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Benign

-0.74

PhyloP100

5.7

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.028

D;D;D

Vest4

0.81

MVP

0.44

MPC

0.70

ClinPred

1.0

GERP RS

4.8

PromoterAI

0.038

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.80

gMVP

0.53

Mutation Taster

=61/39

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over