11-62664891-A-T

Variant names:

Variant summary

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

The NM_024099.5(LBHD1):c.621T>A(p.Asp207Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000252 in 1,590,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LBHD1
NM_024099.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76

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:

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=0.093317926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBHD1	NM_024099.5 link	c.621T>A	p.Asp207Glu	missense_variant	Exon 5 of 7	ENST00000354588.8	NP_077004.2	Q9BQE6-2A0A024R584
C11orf98	NM_001286086.2 link	c.122T>A	p.Ile41Lys	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.621T>A	p.Asp207Glu	missense_variant	Exon 5 of 7	1	NM_024099.5	ENSP00000346600.3	Q9BQE6-2
C11orf98	ENST00000524958.6 link	c.122T>A	p.Ile41Lys	missense_variant	Exon 2 of 4	2	NM_001286086.2	ENSP00000432523.2	E9PRG8
ENSG00000255432	ENST00000528405.1 link	c.122T>A	p.Ile41Lys	missense_variant	Exon 2 of 4	4		ENSP00000435188.1	E9PLD3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000959

AC:

AN:

208604

Hom.:

AF XY:

0.0000177

AC XY:

AN XY:

112824

show subpopulations

Gnomad AFR exome

AF:

0.000160

Gnomad AMR exome

AF:

0.00

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:

0.00000139

AC:

AN:

1437836

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713136

show subpopulations

Gnomad4 AFR exome

AF:

0.0000606

Gnomad4 AMR exome

AF:

0.00

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

AF:

0.0000131

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000334

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.621T>A (p.D207E) alteration is located in exon 5 (coding exon 4) of the LBHD1 gene. This alteration results from a T to A substitution at nucleotide position 621, causing the aspartic acid (D) at amino acid position 207 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

-0.27

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.058

.;T;.;T

Eigen

Benign

0.089

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.38

.;T;T;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.093

T;T;T;T

MetaSVM

Benign

-0.74

PROVEAN

Uncertain

-3.1

D;D;D;.

REVEL

Benign

0.17

Sift

Benign

0.075

T;T;T;.

Sift4G

Benign

0.31

T;T;T;.

Polyphen

0.042

B;.;B;.

Vest4

0.27

MutPred

0.057

Gain of methylation at R210 (P = 0.1503);.;Gain of methylation at R210 (P = 0.1503);.;

MVP

0.030

MPC

0.13

ClinPred

0.30

GERP RS

4.8

Varity_R

0.43

gMVP

0.0038

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