rs750901662

Variant names:

• chr11-62664857-C-T
• rs750901662
• NM_024099.5:c.655G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_024099.5(LBHD1):​c.655G>A​(p.Glu219Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 1,570,228 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: LBHD1 NM_024099.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.87
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2579981).
• BP6: Variant 11-62664857-C-T is Benign according to our data. Variant chr11-62664857-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3866573.Status of the report is criteria_provided_single_submitter, 1 stars.

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.655G>A	p.Glu219Lys	missense	Exon 5 of 7	NP_077004.2
	C11orf98	NM_001286086.2	MANE Select	c.156G>A	p.Lys52Lys	synonymous	Exon 2 of 4	NP_001273015.1	E9PRG8
	LBHD1	NM_001394599.1		c.1147G>A	p.Glu383Lys	missense	Exon 5 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.655G>A	p.Glu219Lys	missense	Exon 5 of 7	ENSP00000346600.3	Q9BQE6-2
	C11orf98	ENST00000524958.6	TSL:2 MANE Select	c.156G>A	p.Lys52Lys	synonymous	Exon 2 of 4	ENSP00000432523.2	E9PRG8
	ENSG00000255432	ENST00000528405.1	TSL:4	c.156G>A	p.Lys52Lys	synonymous	Exon 2 of 4	ENSP00000435188.1	E9PLD3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152164 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: 0.0000220 AC: 4 AN: 182216 AF XY: 0.0000205

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000735

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000176 AC: 25 AN: 1418064 Hom.: 0 Cov.: 31 AF XY: 0.0000200 AC XY: 14 AN XY: 701438

African (AFR) AF: 0.00 AC: 0 AN: 32400

American (AMR) AF: 0.0000263 AC: 1 AN: 38032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25348

East Asian (EAS) AF: 0.00 AC: 0 AN: 37320

South Asian (SAS) AF: 0.00 AC: 0 AN: 81280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5468

European-Non Finnish (NFE) AF: 0.0000202 AC: 22 AN: 1089260

Other (OTH) AF: 0.0000341 AC: 2 AN: 58644

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74334

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

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000488 Hom.: 0

ExAC AF: 0.0000167 AC: 2

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.18
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.97	T
PhyloP100		2.9
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.38
Sift	Benign	0.044	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.011	B
Vest4		0.67
MutPred		0.12		Gain of ubiquitination at E219 (P = 0.0051)
MVP		0.014
MPC		0.12
ClinPred		0.68	D
GERP RS		3.9
PromoterAI		-0.062	Neutral
Varity_R		0.45
gMVP		0.037
Mutation Taster		=82/18	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: rs750901662; hg19: chr11-62432329;