7-104863366-G-A

Variant names:

• chr7-104863366-G-A
• rs10953454
• NM_199000.3:c.683-42821G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199000.3(LHFPL3):​c.683-42821G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,206 control chromosomes in the GnomAD database, including 2,353 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 0.12 (2353 hom., cov: 32)
• Consequence: LHFPL3 NM_199000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 10 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL3	NM_199000.3	c.683-42821G>A		intron_variant	Intron 2 of 2	ENST00000424859.7	NP_945351.1
LHFPL3	NM_001386065.1	c.*31+17937G>A		intron_variant	Intron 3 of 3		NP_001372994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL3	ENST00000424859.7	c.683-42821G>A		intron_variant	Intron 2 of 2	1	NM_199000.3	ENSP00000393128.2
LHFPL3	ENST00000401970.3	c.*31+17937G>A		intron_variant	Intron 3 of 3	1		ENSP00000385374.3
LHFPL3	ENST00000683240.1	n.*290-42821G>A		intron_variant	Intron 3 of 3			ENSP00000508253.1
LHFPL3	ENST00000684090.1	n.261-42821G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18272 AN: 152088 Hom.: 2339 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.0411

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.121 AC: 18341 AN: 152206 Hom.: 2353 Cov.: 32 AF XY: 0.124 AC XY: 9227 AN XY: 74424

African (AFR) AF: 0.288 AC: 11950 AN: 41502

American (AMR) AF: 0.109 AC: 1672 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3470

East Asian (EAS) AF: 0.435 AC: 2247 AN: 5170

South Asian (SAS) AF: 0.0689 AC: 333 AN: 4830

European-Finnish (FIN) AF: 0.0411 AC: 436 AN: 10612

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0209 AC: 1421 AN: 68012

Other (OTH) AF: 0.105 AC: 221 AN: 2114

Alfa AF: 0.0557 Hom.: 3283

Bravo AF: 0.134

Asia WGS AF: 0.273 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.40
DANN	Benign	0.56
PhyloP100		-0.099
Mutation Taster		=100/0	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: rs10953454; hg19: chr7-104503813;