5-78492111-A-G

Variant names:

• chr5-78492111-A-G
• rs11952677
• NM_005779.3:c.431-2958T>C

Variant summary

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

The NM_005779.3(LHFPL2):​c.431-2958T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,074 control chromosomes in the GnomAD database, including 3,910 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 0.20 (3910 hom., cov: 32)
• Consequence: LHFPL2 NM_005779.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL2	NM_005779.3	c.431-2958T>C		intron_variant	Intron 4 of 4	ENST00000380345.7	NP_005770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL2	ENST00000380345.7	c.431-2958T>C		intron_variant	Intron 4 of 4	5	NM_005779.3	ENSP00000369702.2
LHFPL2	ENST00000515007.6	c.431-2958T>C		intron_variant	Intron 2 of 2	1		ENSP00000425906.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29945 AN: 151956 Hom.: 3909 Cov.: 32

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.197 AC: 29946 AN: 152074 Hom.: 3910 Cov.: 32 AF XY: 0.195 AC XY: 14484 AN XY: 74304

African (AFR) AF: 0.0486 AC: 2018 AN: 41490

American (AMR) AF: 0.195 AC: 2973 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 865 AN: 3472

East Asian (EAS) AF: 0.0320 AC: 166 AN: 5184

South Asian (SAS) AF: 0.120 AC: 579 AN: 4820

European-Finnish (FIN) AF: 0.310 AC: 3267 AN: 10540

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19327 AN: 67974

Other (OTH) AF: 0.213 AC: 449 AN: 2112

Alfa AF: 0.254 Hom.: 3903

Bravo AF: 0.181

Asia WGS AF: 0.0790 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.67
PhyloP100		1.5
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: rs11952677; hg19: chr5-77787934;