rs2086005

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001384474.1(LOXHD1):c.2175C>T(p.Asn725Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,551,864 control chromosomes in the GnomAD database, including 13,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 899 hom., cov: 33)

Exomes 𝑓: 0.13 ( 12301 hom. )

Consequence

LOXHD1
NM_001384474.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.452

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 77
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Fuchs' endothelial dystrophy
Inheritance: AD Classification: LIMITED Submitted by: Illumina

LOXHD1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001384474.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 18-46569511-G-A is Benign according to our data. Variant chr18-46569511-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 47926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.452 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384474.1. 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
	LOXHD1	NM_001384474.1	MANE Select	c.2175C>T	p.Asn725Asn	synonymous	Exon 16 of 41	NP_001371403.1	A0A2R8Y7K4
	LOXHD1	NM_144612.7		c.2175C>T	p.Asn725Asn	synonymous	Exon 16 of 40	NP_653213.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LOXHD1	ENST00000642948.1	MANE Select	c.2175C>T	p.Asn725Asn	synonymous	Exon 16 of 41	ENSP00000496347.1	A0A2R8Y7K4
LOXHD1	ENST00000536736.5	TSL:5	c.2175C>T	p.Asn725Asn	synonymous	Exon 16 of 40	ENSP00000444586.1	F5GZB4
LOXHD1	ENST00000441551.6	TSL:5	c.2175C>T	p.Asn725Asn	synonymous	Exon 16 of 39	ENSP00000387621.2	Q8IVV2-1

Frequencies

GnomAD3 genomes

AF:

0.0916

AC:

13938

AN:

152194

Hom.:

898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0262

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.0901

Gnomad EAS

AF:

0.0416

Gnomad SAS

AF:

0.0528

Gnomad FIN

AF:

0.0452

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.112

GnomAD2 exomes

AF:

0.0942

AC:

15082

AN:

160144

AF XY:

0.0947

show subpopulations

Gnomad AFR exome

AF:

0.0228

Gnomad AMR exome

AF:

0.0759

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.0441

Gnomad FIN exome

AF:

0.0528

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.127

AC:

177356

AN:

1399552

Hom.:

12301

Cov.:

AF XY:

0.125

AC XY:

86361

AN XY:

690282

show subpopulations

African (AFR)

AF:

0.0229

AC:

723

AN:

31598

American (AMR)

AF:

0.0784

AC:

2800

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.0986

AC:

2482

AN:

25182

East Asian (EAS)

AF:

0.0244

AC:

873

AN:

35734

South Asian (SAS)

AF:

0.0588

AC:

4656

AN:

79230

European-Finnish (FIN)

AF:

0.0523

AC:

2587

AN:

49466

Middle Eastern (MID)

AF:

0.109

AC:

623

AN:

5700

European-Non Finnish (NFE)

AF:

0.145

AC:

155959

AN:

1078814

Other (OTH)

AF:

0.114

AC:

6653

AN:

58126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

8052

16103

24155

32206

40258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5556

11112

16668

22224

27780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0915

AC:

13935

AN:

152312

Hom.:

899

Cov.:

AF XY:

0.0858

AC XY:

6391

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0261

AC:

1086

AN:

41580

American (AMR)

AF:

0.104

AC:

1594

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0901

AC:

313

AN:

3472

East Asian (EAS)

AF:

0.0415

AC:

215

AN:

5184

South Asian (SAS)

AF:

0.0530

AC:

256

AN:

4830

European-Finnish (FIN)

AF:

0.0452

AC:

480

AN:

10612

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.140

AC:

9514

AN:

68016

Other (OTH)

AF:

0.111

AC:

235

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

640

1279

1919

2558

3198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.119

Hom.:

1196

Bravo

AF:

0.0936

Asia WGS

AF:

0.0380

AC:

130

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Autosomal recessive nonsyndromic hearing loss 77 (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.7

(source)

DANN

Benign

0.68

PhyloP100

0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over