Genetic Variant LHFPL1:p.Leu11Phe (chrX-112671360-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_178175.4(LHFPL1):c.31C>T(p.Leu11Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,210,376 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.000025 ( 0 hom. 8 hem. )

Consequence

LHFPL1
NM_178175.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

Publications

0 publications found

Variant links:

Genes affected

LHFPL1 (HGNC:6587): (LHFPL tetraspan subfamily member 1) 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 one LHFP-like gene result in deafness in humans and mice, and a second LHFP-like gene is fused to a high-mobility group gene in a translocation-associated lipoma. Alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

LHFPL1 links:

ENSG00000303644 (HGNC:):

ENSG00000303644 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23078674).

BS2

High Hemizygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178175.4. 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
	LHFPL1	NM_178175.4	MANE Select	c.31C>T	p.Leu11Phe	missense	Exon 2 of 4	NP_835469.1	Q86WI0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LHFPL1	ENST00000371968.8	TSL:1 MANE Select	c.31C>T	p.Leu11Phe	missense	Exon 2 of 4	ENSP00000361036.3	Q86WI0-1
LHFPL1	ENST00000864007.1		c.31C>T	p.Leu11Phe	missense	Exon 2 of 4	ENSP00000534066.1
LHFPL1	ENST00000864010.1		c.31C>T	p.Leu11Phe	missense	Exon 2 of 4	ENSP00000534070.1

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

112164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000545

AC:

AN:

183384

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.000684

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1098159

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

363519

show subpopulations

African (AFR)

AF:

0.000644

AC:

AN:

26401

American (AMR)

AF:

0.0000284

AC:

AN:

35205

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40514

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

842070

Other (OTH)

AF:

0.000108

AC:

AN:

46095

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

112217

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

AN XY:

34377

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

30906

American (AMR)

AF:

0.00

AC:

AN:

10627

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3568

South Asian (SAS)

AF:

0.00

AC:

AN:

2667

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6145

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53224

Other (OTH)

AF:

0.00

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.76

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.3

PhyloP100

1.2

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.31

Sift

Benign

0.13

Sift4G

Benign

0.12

Polyphen

0.96

Vest4

0.19

MVP

0.54

MPC

0.12

ClinPred

0.065

GERP RS

4.6

Varity_R

0.14

gMVP

0.82

Mutation Taster

=75/25

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over