7-104702290-C-T

Variant names:

• chr7-104702290-C-T
• rs4730037
• NM_199000.3:c.446-34385C>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.446-34385C>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
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199000.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHFPL3	NM_199000.3	MANE Select	c.446-34385C>T		intron	N/A	NP_945351.1
	LHFPL3	NM_001386065.1		c.446-34385C>T		intron	N/A	NP_001372994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHFPL3	ENST00000424859.7	TSL:1 MANE Select	c.446-34385C>T		intron	N/A	ENSP00000393128.2
	LHFPL3	ENST00000401970.3	TSL:1	c.446-34385C>T		intron	N/A	ENSP00000385374.3
	LHFPL3	ENST00000683240.1		n.*53-34385C>T		intron	N/A	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

African (AFR) AF: 0.706 AC: 29273 AN: 41462

American (AMR) AF: 0.657 AC: 10042 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2541 AN: 3470

East Asian (EAS) AF: 0.595 AC: 3066 AN: 5152

South Asian (SAS) AF: 0.429 AC: 2069 AN: 4820

European-Finnish (FIN) AF: 0.611 AC: 6450 AN: 10564

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.629 AC: 42768 AN: 67956

Other (OTH) AF: 0.652 AC: 1377 AN: 2112

Alfa AF: 0.625 Hom.: 17481

Bravo AF: 0.657

Asia WGS AF: 0.573 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.40
DANN	Benign	0.54
PhyloP100		-1.2
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: rs4730037; hg19: chr7-104342737;