7-104702290-C-T

Variant names:

• chr7-104702290-C-T
• rs4730037
• NM_199000.3:c.446-34385C>T

Variant summary

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

The NM_199000.3(LHFPL3):​c.446-34385C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,024 control chromosomes in the GnomAD database, including 32,218 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 0.65 (32218 hom., cov: 31)
• Consequence: LHFPL3 NM_199000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL3	NM_199000.3	c.446-34385C>T		intron_variant	Intron 1 of 2	ENST00000424859.7	NP_945351.1
LHFPL3	NM_001386065.1	c.446-34385C>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.446-34385C>T		intron_variant	Intron 1 of 2	1	NM_199000.3	ENSP00000393128.2
LHFPL3	ENST00000401970.3	c.446-34385C>T		intron_variant	Intron 1 of 3	1		ENSP00000385374.3
LHFPL3	ENST00000683240.1	n.*53-34385C>T		intron_variant	Intron 2 of 3			ENSP00000508253.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98334 AN: 151906 Hom.: 32186 Cov.: 31

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.647 AC: 98419 AN: 152024 Hom.: 32218 Cov.: 31 AF XY: 0.643 AC XY: 47760 AN XY: 74308

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.652

Alfa AF: 0.624 Hom.: 15712

Bravo AF: 0.657

Asia WGS AF: 0.573 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.40
DANN	Benign	0.54

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: rs4730037; hg19: chr7-104342737;