rs67478220

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

LHFPL5 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 67

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182548.4. 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
	LHFPL5	NM_182548.4	MANE Select	c.-296_-295delAG		5_prime_UTR	Exon 1 of 4	NP_872354.1	Q8TAF8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHFPL5	ENST00000360215.3	TSL:1 MANE Select	c.-296_-295delAG		5_prime_UTR	Exon 1 of 4	ENSP00000353346.1	Q8TAF8
	LHFPL5	ENST00000651132.1		c.-134-162_-134-161delAG		intron	N/A	ENSP00000498322.1	Q8TAF8
	LHFPL5	ENST00000651994.1		n.-296_-295delAG		non_coding_transcript_exon	Exon 1 of 4	ENSP00000498310.1	A0A494BZZ7

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

African (AFR) AF: 0.370 AC: 2796 AN: 7550

American (AMR) AF: 0.0618 AC: 605 AN: 9796

Ashkenazi Jewish (ASJ) AF: 0.0788 AC: 564 AN: 7156

East Asian (EAS) AF: 0.00351 AC: 50 AN: 14232

South Asian (SAS) AF: 0.144 AC: 4156 AN: 28774

European-Finnish (FIN) AF: 0.0533 AC: 676 AN: 12682

Middle Eastern (MID) AF: 0.131 AC: 134 AN: 1022

European-Non Finnish (NFE) AF: 0.0443 AC: 6189 AN: 139842

Other (OTH) AF: 0.0718 AC: 965 AN: 13436

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

African (AFR) AF: 0.368 AC: 15240 AN: 41392

American (AMR) AF: 0.0754 AC: 1152 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3470

East Asian (EAS) AF: 0.00875 AC: 45 AN: 5140

South Asian (SAS) AF: 0.144 AC: 694 AN: 4808

European-Finnish (FIN) AF: 0.0602 AC: 638 AN: 10602

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0461 AC: 3134 AN: 67924

Other (OTH) AF: 0.136 AC: 286 AN: 2110

Alfa AF: 0.104 Hom.: 218

Bravo AF: 0.150

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hearing loss, autosomal recessive (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs67478220; hg19: chr6-35773149;