6-35804978-G-A

Variant names:

• chr6-35804978-G-A
• rs2766524
• ENST00000651132.1:c.-134-559G>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL5	ENST00000651132.1	c.-134-559G>A		intron_variant	Intron 3 of 6			ENSP00000498322.1

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

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;