chr11-62663240-C-T

Variant names:

• chr11-62663240-C-T
• rs1286160337
• NM_024099.5:c.757G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024099.5(LBHD1):​c.757G>A​(p.Gly253Arg) 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 1,461,866 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LBHD1 NM_024099.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.50
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23718655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024099.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBHD1	NM_024099.5	MANE Select	c.757G>A	p.Gly253Arg	missense	Exon 6 of 7	NP_077004.2
	C11orf98	NM_001286086.2	MANE Select	c.258G>A	p.Met86Ile	missense	Exon 3 of 4	NP_001273015.1	E9PRG8
	LBHD1	NM_001394599.1		c.1249G>A	p.Gly417Arg	missense	Exon 6 of 7	NP_001381528.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBHD1	ENST00000354588.8	TSL:1 MANE Select	c.757G>A	p.Gly253Arg	missense	Exon 6 of 7	ENSP00000346600.3	Q9BQE6-2
	C11orf98	ENST00000524958.6	TSL:2 MANE Select	c.258G>A	p.Met86Ile	missense	Exon 3 of 4	ENSP00000432523.2	E9PRG8
	ENSG00000255432	ENST00000528405.1	TSL:4	c.258G>A	p.Met86Ile	missense	Exon 3 of 4	ENSP00000435188.1	E9PLD3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461866 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.98	T
PhyloP100		3.5
PROVEAN	Pathogenic	-7.3	D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.080		Gain of solvent accessibility (P = 0.019)
MVP		0.099
MPC		0.17
ClinPred		0.98	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.0072
Mutation Taster		=84/16	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: rs1286160337; hg19: chr11-62430712;