6-35805372-AAG-A

Variant names:

• chr6-35805372-AAG-A
• rs67478220
• NM_182548.4:c.-296_-295delAG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_182548.4(LHFPL5):​c.-296_-295delAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0973 in 386,428 control chromosomes in the GnomAD database, including 4,190 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (3043 hom., cov: 30)
  • Exomes 𝑓: 0.069 (1147 hom.)
• Consequence: LHFPL5 NM_182548.4 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.241

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 -16 ACMG points.

• BP6: Variant 6-35805372-AAG-A is Benign according to our data. Variant chr6-35805372-AAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 356481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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
LHFPL5	NM_182548.4	c.-296_-295delAG		5_prime_UTR_variant	Exon 1 of 4	ENST00000360215.3	NP_872354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL5	ENST00000360215	c.-296_-295delAG		5_prime_UTR_variant	Exon 1 of 4	1	NM_182548.4	ENSP00000353346.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21392 AN: 151820 Hom.: 3020 Cov.: 30

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0755

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.00873

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.0688 AC: 16135 AN: 234490 Hom.: 1147 AF XY: 0.0741 AC XY: 9155 AN XY: 123624

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.0618

Gnomad4 ASJ exome AF: 0.0788

Gnomad4 EAS exome AF: 0.00351

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.0533

Gnomad4 NFE exome AF: 0.0443

Gnomad4 OTH exome AF: 0.0718

GnomAD4 genome AF: 0.141 AC: 21467 AN: 151938 Hom.: 3043 Cov.: 30 AF XY: 0.141 AC XY: 10469 AN XY: 74300

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.0754

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.00875

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.136

Alfa AF: 0.104 Hom.: 218

Bravo AF: 0.150

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Nov 05, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hearing loss, autosomal recessive Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs67478220; hg19: chr6-35773149;