5-78520604-C-T

Position:

• chr5-78520604-C-T

Variant summary

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

The NM_005779.3(LHFPL2):​c.-185-10206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,094 control chromosomes in the GnomAD database, including 17,398 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 0.47 (17398 hom., cov: 33)
• Consequence: LHFPL2 NM_005779.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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]

LHFPL2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHFPL2	NM_005779.3	c.-185-10206G>A		intron_variant		ENST00000380345.7	NP_005770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHFPL2	ENST00000380345.7	c.-185-10206G>A		intron_variant		5	NM_005779.3	ENSP00000369702.2

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72077 AN: 151976 Hom.: 17388 Cov.: 33

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.474 AC: 72134 AN: 152094 Hom.: 17398 Cov.: 33 AF XY: 0.471 AC XY: 35008 AN XY: 74342

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.483

Alfa AF: 0.509 Hom.: 24835

Bravo AF: 0.456

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.42

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: rs12189541; hg19: chr5-77816427;