Variant rs143514947 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001384474.1(LOXHD1):c.6183-11delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,549,790 control chromosomes in the GnomAD database, including 75,903 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5227 hom., cov: 23)

Exomes 𝑓: 0.31 ( 70676 hom. )

Consequence

LOXHD1
NM_001384474.1 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.360

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 -16 ACMG points.

BP6

Variant 18-46483755-AC-A is Benign according to our data. Variant chr18-46483755-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 262524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOXHD1	NM_001384474.1 linkuse as main transcript	c.6183-11delG		intron_variant		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.6183-11delG		intron_variant			NM_001384474.1	ENSP00000496347.1		A0A2R8Y7K4

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35887

AN:

151880

Hom.:

5228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0777

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.0112

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.259

GnomAD3 exomes

AF:

0.263

AC:

41144

AN:

156302

Hom.:

6105

AF XY:

0.267

AC XY:

22012

AN XY:

82588

show subpopulations

Gnomad AFR exome

AF:

0.0685

Gnomad AMR exome

AF:

0.251

Gnomad ASJ exome

AF:

0.246

Gnomad EAS exome

AF:

0.00826

Gnomad SAS exome

AF:

0.258

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.310

AC:

433923

AN:

1397792

Hom.:

70676

Cov.:

AF XY:

0.310

AC XY:

213431

AN XY:

689212

show subpopulations

Gnomad4 AFR exome

AF:

0.0681

Gnomad4 AMR exome

AF:

0.258

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.00915

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.337

Gnomad4 OTH exome

AF:

0.286

GnomAD4 genome

AF:

0.236

AC:

35876

AN:

151998

Hom.:

5227

Cov.:

AF XY:

0.234

AC XY:

17393

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.0775

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.250

Gnomad4 EAS

AF:

0.0112

Gnomad4 SAS

AF:

0.252

Gnomad4 FIN

AF:

0.306

Gnomad4 NFE

AF:

0.330

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.185

Hom.:

696

Bravo

AF:

0.224

Asia WGS

AF:

0.160

AC:

558

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive nonsyndromic hearing loss 77

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 27, 2019

- -

Hearing loss, autosomal recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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