13-39554708-T-C

Variant names:

• chr13-39554708-T-C
• rs9315703
• NM_005780.3:c.385+46124A>G

Variant summary

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

The NM_005780.3(LHFPL6):​c.385+46124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,052 control chromosomes in the GnomAD database, including 11,285 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 0.37 (11285 hom., cov: 32)
• Consequence: LHFPL6 NM_005780.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 3 publications found

Genes affected

LHFPL6 (HGNC:6586): (LHFPL tetraspan subfamily member 6) 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. This gene is fused to a high-mobility group gene in a translocation-associated lipoma. Mutations in another LHFP-like gene result in deafness in humans and mice. Alternatively spliced transcript variants have been found; however, their full-length nature is not known. [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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL6	NM_005780.3	c.385+46124A>G		intron_variant	Intron 2 of 3	ENST00000379589.4	NP_005771.1
LHFPL6	XM_011534861.2	c.385+46124A>G		intron_variant	Intron 2 of 3		XP_011533163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL6	ENST00000379589.4	c.385+46124A>G		intron_variant	Intron 2 of 3	1	NM_005780.3	ENSP00000368908.3
LHFPL6	ENST00000648377.1	n.385+46124A>G		intron_variant	Intron 2 of 13			ENSP00000496801.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56975 AN: 151934 Hom.: 11286 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.375 AC: 56973 AN: 152052 Hom.: 11285 Cov.: 32 AF XY: 0.375 AC XY: 27854 AN XY: 74310

African (AFR) AF: 0.265 AC: 10983 AN: 41474

American (AMR) AF: 0.318 AC: 4857 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1551 AN: 3464

East Asian (EAS) AF: 0.292 AC: 1509 AN: 5176

South Asian (SAS) AF: 0.451 AC: 2170 AN: 4810

European-Finnish (FIN) AF: 0.463 AC: 4881 AN: 10550

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29648 AN: 67988

Other (OTH) AF: 0.383 AC: 809 AN: 2112

Alfa AF: 0.414 Hom.: 7579

Bravo AF: 0.355

Asia WGS AF: 0.355 AC: 1238 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	0.33
DANN	Benign	0.54
PhyloP100		-1.7
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: rs9315703; hg19: chr13-40128845;