7-104789609-A-G

Variant names:

• chr7-104789609-A-G
• rs4730049
• NM_199000.3:c.682+52698A>G

Variant summary

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

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LHFPL3	NM_199000.3	c.682+52698A>G		intron_variant	Intron 2 of 2	ENST00000424859.7	NP_945351.1
LHFPL3	NM_001386065.1	c.682+52698A>G		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	c.682+52698A>G		intron_variant	Intron 2 of 2	1	NM_199000.3	ENSP00000393128.2

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

African (AFR) AF: 0.482 AC: 19939 AN: 41364

American (AMR) AF: 0.519 AC: 7900 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1831 AN: 3468

East Asian (EAS) AF: 0.820 AC: 4238 AN: 5168

South Asian (SAS) AF: 0.472 AC: 2265 AN: 4794

European-Finnish (FIN) AF: 0.530 AC: 5588 AN: 10540

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.491 AC: 33343 AN: 67886

Other (OTH) AF: 0.514 AC: 1081 AN: 2104

Alfa AF: 0.495 Hom.: 59349

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
PhyloP100		-2.1
Mutation Taster		=99/1	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: rs4730049; hg19: chr7-104430056;