rs9957285

chr18-46503844-C-Achr18-46503844-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384474.1(LOXHD1):c.5878+1994G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,956 control chromosomes in the GnomAD database, including 6,896 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6896 hom., cov: 31)
• Consequence: LOXHD1 NM_001384474.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXHD1	NM_001384474.1	c.5878+1994G>T		intron_variant		ENST00000642948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXHD1	ENST00000642948.1	c.5878+1994G>T		intron_variant			NM_001384474.1	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40640 AN: 151840 Hom.: 6888 Cov.: 31

Gnomad AFR AF: 0.0797

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.298

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.268 AC: 40651 AN: 151956 Hom.: 6896 Cov.: 31 AF XY: 0.271 AC XY: 20114 AN XY: 74262

Gnomad4 AFR AF: 0.0795

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.301

Alfa AF: 0.306 Hom.: 4446

Bravo AF: 0.267

Asia WGS AF: 0.381 AC: 1325 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.1
Dann	Benign	0.75

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

Other links and lift over

dbSNP: rs9957285; hg19: chr18-44083807;