7-104586872-A-T

Variant names:

• chr7-104586872-A-T
• rs4730025
• NM_199000.3:c.446-149803A>T

Variant summary

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

The NM_199000.3(LHFPL3):​c.446-149803A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,108 control chromosomes in the GnomAD database, including 2,867 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 0.19 (2867 hom., cov: 33)
• Consequence: LHFPL3 NM_199000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• 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]

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 = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL3	NM_199000.3	c.446-149803A>T		intron_variant	Intron 1 of 2	ENST00000424859.7	NP_945351.1
LHFPL3	NM_001386065.1	c.446-149803A>T		intron_variant	Intron 1 of 3		NP_001372994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL3	ENST00000424859.7	c.446-149803A>T		intron_variant	Intron 1 of 2	1	NM_199000.3	ENSP00000393128.2
LHFPL3	ENST00000401970.3	c.446-149803A>T		intron_variant	Intron 1 of 3	1		ENSP00000385374.3
LHFPL3	ENST00000683240.1	n.*53-149803A>T		intron_variant	Intron 2 of 3			ENSP00000508253.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28377 AN: 151990 Hom.: 2864 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.187 AC: 28398 AN: 152108 Hom.: 2867 Cov.: 33 AF XY: 0.192 AC XY: 14299 AN XY: 74354

African (AFR) AF: 0.183 AC: 7583 AN: 41498

American (AMR) AF: 0.200 AC: 3047 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3468

East Asian (EAS) AF: 0.378 AC: 1952 AN: 5158

South Asian (SAS) AF: 0.178 AC: 860 AN: 4828

European-Finnish (FIN) AF: 0.260 AC: 2755 AN: 10592

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10995 AN: 68000

Other (OTH) AF: 0.204 AC: 430 AN: 2110

Alfa AF: 0.0870 Hom.: 130

Bravo AF: 0.182

Asia WGS AF: 0.338 AC: 1173 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	0.81
DANN	Benign	0.68
PhyloP100		0.030
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: rs4730025; hg19: chr7-104227319;