Variant 18-46524777-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001384474.1(LOXHD1):c.4671G>A(p.Leu1557=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,551,676 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 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

LOXHD1
NM_001384474.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.812

Variant links:

Genes affected

LOXHD1 (HGNC:26521): (lipoxygenase homology PLAT domains 1) This gene encodes a highly conserved protein consisting entirely of PLAT (polycystin/lipoxygenase/alpha-toxin) domains, thought to be involved in targeting proteins to the plasma membrane. Studies in mice show that this gene is expressed in the mechanosensory hair cells in the inner ear, and mutations in this gene lead to auditory defects, indicating that this gene is essential for normal hair cell function. Screening of human families segregating deafness identified a mutation in this gene which causes DFNB77, a progressive form of autosomal-recessive nonsyndromic hearing loss (ARNSHL). Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2010]

LOXHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 18-46524777-C-T is Benign according to our data. Variant chr18-46524777-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 504967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-46524777-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.812 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOXHD1	NM_001384474.1 linkuse as main transcript	c.4671G>A	p.Leu1557=	synonymous_variant	30/41	ENST00000642948.1	NP_001371403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOXHD1	ENST00000642948.1 linkuse as main transcript	c.4671G>A	p.Leu1557=	synonymous_variant	30/41		NM_001384474.1	ENSP00000496347	P1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000120

AC:

AN:

158016

Hom.:

AF XY:

0.000144

AC XY:

AN XY:

83204

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.000471

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000878

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000989

Gnomad OTH exome

AF:

0.000449

GnomAD4 exome

AF:

0.000106

AC:

148

AN:

1399412

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

690210

show subpopulations

Gnomad4 AFR exome

AF:

0.000222

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000649

Gnomad4 OTH exome

AF:

0.000362

GnomAD4 genome

AF:

0.000105

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.0000982

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 18, 2016

p.Leu1557Leu in exon 30 of LOXHD1: This variant is not expected to have clinical significance because it does not alter an amino acid residue, and it is not loc ated within the splice consensus sequence. It has been identified in 1/7914 Sou th Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs763078543). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.54

DANN

Benign

0.69

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