rs4530975

Variant names:

• chr7-104774968-C-T
• rs4530975
• NM_199000.3:c.682+38057C>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.682+38057C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,170 control chromosomes in the GnomAD database, including 3,803 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 0.21 (3803 hom., cov: 33)
• Consequence: LHFPL3 NM_199000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 5 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]

LHFPL3-AS1 (HGNC:40341): (LHFPL3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL3	NM_199000.3	c.682+38057C>T		intron_variant	Intron 2 of 2	ENST00000424859.7	NP_945351.1
LHFPL3	NM_001386065.1	c.682+38057C>T		intron_variant	Intron 2 of 3		NP_001372994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL3	ENST00000424859.7	c.682+38057C>T		intron_variant	Intron 2 of 2	1	NM_199000.3	ENSP00000393128.2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32462 AN: 152052 Hom.: 3796 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.214 AC: 32494 AN: 152170 Hom.: 3803 Cov.: 33 AF XY: 0.213 AC XY: 15845 AN XY: 74390

African (AFR) AF: 0.119 AC: 4959 AN: 41516

American (AMR) AF: 0.257 AC: 3931 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 777 AN: 3470

East Asian (EAS) AF: 0.0958 AC: 497 AN: 5188

South Asian (SAS) AF: 0.233 AC: 1121 AN: 4818

European-Finnish (FIN) AF: 0.222 AC: 2351 AN: 10582

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18069 AN: 67986

Other (OTH) AF: 0.229 AC: 485 AN: 2114

Alfa AF: 0.254 Hom.: 10260

Bravo AF: 0.211

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.64
PhyloP100		-0.11
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: rs4530975; hg19: chr7-104415415;