Menu
GeneBe

rs779218726

chr18-46485117-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001384474.1(LOXHD1):c.6084C>T(p.Gly2028=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000071 in 1,549,088 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 0.000067 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

LOXHD1
NM_001384474.1 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.626
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 18-46485117-G-A is Benign according to our data. Variant chr18-46485117-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 517332.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.626 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LOXHD1NM_001384474.1 linkuse as main transcriptc.6084C>T p.Gly2028= synonymous_variant 39/41 ENST00000642948.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LOXHD1ENST00000642948.1 linkuse as main transcriptc.6084C>T p.Gly2028= synonymous_variant 39/41 NM_001384474.1 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000668
AC:
10
AN:
149608
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000247
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000135
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000218
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000887
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000822
AC:
13
AN:
158176
Hom.:
0
AF XY:
0.0000838
AC XY:
7
AN XY:
83494
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000917
Gnomad SAS exome
AF:
0.0000878
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000162
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000715
AC:
100
AN:
1399364
Hom.:
0
Cov.:
35
AF XY:
0.0000652
AC XY:
45
AN XY:
690202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000280
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.000164
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000686
Gnomad4 OTH exome
AF:
0.000189
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000668
AC:
10
AN:
149724
Hom.:
0
Cov.:
30
AF XY:
0.0000686
AC XY:
5
AN XY:
72896
show subpopulations
Gnomad4 AFR
AF:
0.0000246
Gnomad4 AMR
AF:
0.000135
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000219
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000887
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000987
Hom.:
0
Bravo
AF:
0.0000604

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineApr 20, 2017p.Gly1966Gly in exon 38 of LOXHD1: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. This variant has been identified in 1/927 0 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs779218726). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
7.4
Dann
Benign
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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.

Other links and lift over

dbSNP: rs779218726; hg19: chr18-44065080; COSMIC: COSV56072575; API