rs784420

Variant names:

• chr5-78691701-A-G
• rs784420
• ENST00000514587.1:n.402-59333T>C

Variant summary

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

The ENST00000514587.1(LHFPL2):​n.402-59333T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,188 control chromosomes in the GnomAD database, including 4,942 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 0.22 (4942 hom., cov: 32)
• Consequence: LHFPL2 ENST00000514587.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 9 publications found

Genes affected

LHFPL2 (HGNC:6588): (LHFPL tetraspan subfamily member 2) 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. Alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

LOC124900191 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124900191	XR_007058832.1	n.489+26383T>C		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL2	ENST00000514587.1	n.402-59333T>C		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33999 AN: 152070 Hom.: 4934 Cov.: 32

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.00866

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.224 AC: 34015 AN: 152188 Hom.: 4942 Cov.: 32 AF XY: 0.226 AC XY: 16800 AN XY: 74410

African (AFR) AF: 0.0555 AC: 2306 AN: 41568

American (AMR) AF: 0.358 AC: 5459 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1220 AN: 3472

East Asian (EAS) AF: 0.00868 AC: 45 AN: 5186

South Asian (SAS) AF: 0.248 AC: 1195 AN: 4822

European-Finnish (FIN) AF: 0.284 AC: 3011 AN: 10584

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19885 AN: 67976

Other (OTH) AF: 0.232 AC: 490 AN: 2114

Alfa AF: 0.277 Hom.: 26451

Bravo AF: 0.222

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs784420; hg19: chr5-77987524;