chr11-62664937-A-C

Variant names:

• chr11-62664937-A-C
• rs760929972
• NM_024099.5:c.575T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024099.5(LBHD1):​c.575T>G​(p.Val192Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,608,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LBHD1 NM_024099.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0240
• Publications: 0 publications found

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]

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]

ENSG00000255432 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1261673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBHD1	NM_024099.5	c.575T>G	p.Val192Gly	missense_variant	Exon 5 of 7	ENST00000354588.8	NP_077004.2
C11orf98	NM_001286086.2	c.76T>G	p.Leu26Val	missense_variant	Exon 2 of 4	ENST00000524958.6	NP_001273015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBHD1	ENST00000354588.8	c.575T>G	p.Val192Gly	missense_variant	Exon 5 of 7	1	NM_024099.5	ENSP00000346600.3
C11orf98	ENST00000524958.6	c.76T>G	p.Leu26Val	missense_variant	Exon 2 of 4	2	NM_001286086.2	ENSP00000432523.2
ENSG00000255432	ENST00000528405.1	c.76T>G	p.Leu26Val	missense_variant	Exon 2 of 4	4		ENSP00000435188.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152084 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000420 AC: 1 AN: 238360 AF XY: 0.00000772

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000930

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456440 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 724122

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 43924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.00 AC: 0 AN: 85478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52348

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5752

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109934

Other (OTH) AF: 0.00 AC: 0 AN: 60110

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152084 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74286

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.575T>G (p.V192G) alteration is located in exon 5 (coding exon 4) of the LBHD1 gene. This alteration results from a T to G substitution at nucleotide position 575, causing the valine (V) at amino acid position 192 to be replaced by a glycine (G). 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	0.22
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.078	.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.97	T
PhyloP100		0.024
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.048	D;D;D
Sift4G	Benign	0.35	T;T;T
Vest4		0.51
MVP		0.12
MPC		1.1
ClinPred		0.86	D
GERP RS		-2.0
PromoterAI		0.039	Neutral
Varity_R		0.57
gMVP		0.39
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs760929972; hg19: chr11-62432409;