rs4367471

Positions:

• chr7-104742426-T-C

Variant summary

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

The NM_199000.3(LHFPL3):​c.682+5515T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,242 control chromosomes in the GnomAD database, including 2,678 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 0.16 (2678 hom., cov: 32)
• Consequence: LHFPL3 NM_199000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHFPL3	NM_199000.3	c.682+5515T>C		intron_variant		ENST00000424859.7	NP_945351.1
LHFPL3	NM_001386065.1	c.682+5515T>C		intron_variant			NP_001372994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHFPL3	ENST00000424859.7	c.682+5515T>C		intron_variant		1	NM_199000.3	ENSP00000393128.2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25051 AN: 152124 Hom.: 2680 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0648

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.165 AC: 25045 AN: 152242 Hom.: 2678 Cov.: 32 AF XY: 0.170 AC XY: 12617 AN XY: 74416

Gnomad4 AFR AF: 0.0426

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0642

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.162

Alfa AF: 0.207 Hom.: 2215

Bravo AF: 0.154

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.1
DANN	Benign	0.76

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: rs4367471; hg19: chr7-104382873; COSMIC: COSV67824759;