Variant rs1450425 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001384474.1(LOXHD1):c.4530+107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 1,356,964 control chromosomes in the GnomAD database, including 346,192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33931 hom., cov: 29)

Exomes 𝑓: 0.72 ( 312261 hom. )

Consequence

LOXHD1
NM_001384474.1 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.88

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 18-46529070-T-C is Benign according to our data. Variant chr18-46529070-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 191090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.727 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.4530+107A>G		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.4530+107A>G		intron_variant			NM_001384474.1	ENSP00000496347	P1

Frequencies

GnomAD3 genomes

AF:

0.663

AC:

100528

AN:

151542

Hom.:

33920

Cov.:

show subpopulations

Gnomad AFR

AF:

0.547

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.648

Gnomad ASJ

AF:

0.708

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.676

Gnomad FIN

AF:

0.734

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.732

Gnomad OTH

AF:

0.669

GnomAD4 exome

AF:

0.718

AC:

865381

AN:

1205304

Hom.:

312261

AF XY:

0.718

AC XY:

428587

AN XY:

596972

show subpopulations

Gnomad4 AFR exome

AF:

0.539

Gnomad4 AMR exome

AF:

0.642

Gnomad4 ASJ exome

AF:

0.701

Gnomad4 EAS exome

AF:

0.620

Gnomad4 SAS exome

AF:

0.680

Gnomad4 FIN exome

AF:

0.733

Gnomad4 NFE exome

AF:

0.733

Gnomad4 OTH exome

AF:

0.706

GnomAD4 genome

AF:

0.663

AC:

100580

AN:

151660

Hom.:

33931

Cov.:

AF XY:

0.662

AC XY:

49070

AN XY:

74086

show subpopulations

Gnomad4 AFR

AF:

0.547

Gnomad4 AMR

AF:

0.648

Gnomad4 ASJ

AF:

0.708

Gnomad4 EAS

AF:

0.590

Gnomad4 SAS

AF:

0.676

Gnomad4 FIN

AF:

0.734

Gnomad4 NFE

AF:

0.732

Gnomad4 OTH

AF:

0.668

Alfa

AF:

0.718

Hom.:

51748

Bravo

AF:

0.650

Asia WGS

AF:

0.660

AC:

2298

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Sep 28, 2016

- -

Autosomal recessive nonsyndromic hearing loss 77

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.43

DANN

Benign

0.41

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