dbSNP rs4073894: LHFPL3:c.683-79670G>A (chr7-104826517-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_199000.3(LHFPL3):c.683-79670G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 161,208 control chromosomes in the GnomAD database, including 2,584 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2369 hom., cov: 32)

Exomes 𝑓: 0.20 ( 215 hom. )

Consequence

LHFPL3
NM_199000.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.711

Publications

10 publications found

Variant links:

Genes affected

LHFPL3 (HGNC:6589): (LHFPL tetraspan subfamily member 3) 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. A partial gene fragment named LHFPL4 corresponds to a portion of the first exon of this gene. [provided by RefSeq, Jul 2008]

LHFPL3 links:

ENSG00000237606 (HGNC:):

ENSG00000237606 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL3	NM_199000.3 link	c.683-79670G>A		intron_variant	Intron 2 of 2	ENST00000424859.7	NP_945351.1
LHFPL3	NM_001386065.1 link	c.683-18865G>A		intron_variant	Intron 2 of 3		NP_001372994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL3	ENST00000424859.7 link	c.683-79670G>A		intron_variant	Intron 2 of 2	1	NM_199000.3	ENSP00000393128.2

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25444

AN:

151678

Hom.:

2364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.0619

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.177

GnomAD4 exome

AF:

0.197

AC:

1858

AN:

9412

Hom.:

215

Cov.:

AF XY:

0.202

AC XY:

939

AN XY:

4638

show subpopulations

African (AFR)

AF:

0.313

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.200

AC:

AN:

South Asian (SAS)

AF:

0.0919

AC:

AN:

838

European-Finnish (FIN)

AF:

0.208

AC:

1670

AN:

8046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.208

AC:

AN:

394

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

129

193

258

322

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:

0.168

AC:

25451

AN:

151796

Hom.:

2369

Cov.:

AF XY:

0.163

AC XY:

12126

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.133

AC:

5492

AN:

41248

American (AMR)

AF:

0.133

AC:

2027

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

782

AN:

3464

East Asian (EAS)

AF:

0.0622

AC:

322

AN:

5176

South Asian (SAS)

AF:

0.102

AC:

493

AN:

4810

European-Finnish (FIN)

AF:

0.197

AC:

2084

AN:

10568

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13652

AN:

67958

Other (OTH)

AF:

0.175

AC:

369

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1068

2137

3205

4274

5342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<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:

0.191

Hom.:

4928

Bravo

AF:

0.162

Asia WGS

AF:

0.0880

AC:

306

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

4.5

(source)

DANN

Benign

0.49

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over