rs10273020

Positions:

• chr7-104699102-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.446-37573A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,078 control chromosomes in the GnomAD database, including 9,270 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 0.34 (9270 hom., cov: 32)
• Consequence: LHFPL3 NM_199000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHFPL3	NM_199000.3	c.446-37573A>G		intron_variant		ENST00000424859.7
LHFPL3	NM_001386065.1	c.446-37573A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHFPL3	ENST00000424859.7	c.446-37573A>G		intron_variant		1	NM_199000.3	P1
LHFPL3	ENST00000401970.3	c.446-37573A>G		intron_variant		1
LHFPL3	ENST00000683240.1	c.*53-37573A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51873 AN: 151958 Hom.: 9263 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.341 AC: 51905 AN: 152078 Hom.: 9270 Cov.: 32 AF XY: 0.345 AC XY: 25680 AN XY: 74330

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.337

Alfa AF: 0.375 Hom.: 5038

Bravo AF: 0.330

Asia WGS AF: 0.389 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.83

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: rs10273020; hg19: chr7-104339549;