6-35804978-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000651132.1(LHFPL5):c.-134-559G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 151,988 control chromosomes in the GnomAD database, including 3,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (3046 hom., cov: 31)
• Consequence: LHFPL5 ENST00000651132.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0420

Genes affected

LHFPL5 (HGNC:21253): (LHFPL tetraspan subfamily member 5) This gene is a member of the lipoma HMGIC fusion partner (LHFP) gene family, which is a subset of the superfamily of tetraspan transmembrane protein encoding genes. Mutations in this gene result in deafness in humans, and a mutation in a similar gene in mice results in deafness and vestibular dysfunction with severe degeneration of the organ of Corti. It is proposed to function in hair bundle morphogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-35804978-G-A is Benign according to our data. Variant chr6-35804978-G-A is described in ClinVar as [Benign]. Clinvar id is 1265161.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHFPL5	ENST00000651132.1	c.-134-559G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21365 AN: 151870 Hom.: 3023 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0757

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.00886

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.141 AC: 21441 AN: 151988 Hom.: 3046 Cov.: 31 AF XY: 0.141 AC XY: 10459 AN XY: 74298

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.0756

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.00888

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.0460

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0752 Hom.: 351

Bravo AF: 0.150

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.3
Dann	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2766524; hg19: chr6-35772755;