7-104789609-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199000.3(LHFPL3):c.682+52698A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,756 control chromosomes in the GnomAD database, including 19,753 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 0.51 (19753 hom., cov: 31)
• Consequence: LHFPL3 NM_199000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

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-AS1 (HGNC:40341): (LHFPL3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHFPL3	NM_199000.3	c.682+52698A>G		intron_variant		ENST00000424859.7
LHFPL3	NM_001386065.1	c.682+52698A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHFPL3	ENST00000424859.7	c.682+52698A>G		intron_variant		1	NM_199000.3	P1
LHFPL3-AS1	ENST00000449764.5	n.510+10209T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76636 AN: 151638 Hom.: 19726 Cov.: 31

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.508

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.506 AC: 76715 AN: 151756 Hom.: 19753 Cov.: 31 AF XY: 0.507 AC XY: 37616 AN XY: 74160

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.514

Alfa AF: 0.495 Hom.: 37618

Bravo AF: 0.505

Asia WGS AF: 0.647 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.026
Dann	Benign	0.18

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: rs4730049; hg19: chr7-104430056;