11-62664891-A-T

Variant names:

• chr11-62664891-A-T
• rs532701253
• NM_024099.5:c.621T>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.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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.76
• 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=0.093317926).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152122 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.00000959 AC: 2 AN: 208604 AF XY: 0.0000177

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1437836 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 713136

African (AFR) AF: 0.0000606 AC: 2 AN: 33026

American (AMR) AF: 0.00 AC: 0 AN: 40490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25592

East Asian (EAS) AF: 0.00 AC: 0 AN: 38614

South Asian (SAS) AF: 0.00 AC: 0 AN: 83122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100428

Other (OTH) AF: 0.00 AC: 0 AN: 59396

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152240 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74428

African (AFR) AF: 0.0000481 AC: 2 AN: 41562

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000334 Hom.: 0

Bravo AF: 0.0000227

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

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	Pathogenic	0.76
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.058	.;T;.;T
Eigen	Benign	0.089
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.38	.;T;T;T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.093	T;T;T;T
MetaSVM	Benign	-0.74	T
PhyloP100		4.8
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	T
GERP RS		4.8
PromoterAI		0.019	Neutral
Varity_R		0.43
gMVP		0.0038
Mutation Taster		=75/25	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: rs532701253; hg19: chr11-62432363;