13-39375025-A-G

Variant names:

• chr13-39375025-A-G
• rs1186468
• NM_005780.3:c.484+3403T>C

Variant summary

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

The NM_005780.3(LHFPL6):​c.484+3403T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,188 control chromosomes in the GnomAD database, including 37,044 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 0.69 (37044 hom., cov: 33)
• Consequence: LHFPL6 NM_005780.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 7 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005780.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHFPL6	NM_005780.3	MANE Select	c.484+3403T>C		intron	N/A	NP_005771.1	Q9Y693

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHFPL6	ENST00000379589.4	TSL:1 MANE Select	c.484+3403T>C		intron	N/A	ENSP00000368908.3	Q9Y693
	LHFPL6	ENST00000855018.1		c.577+3403T>C		intron	N/A	ENSP00000525077.1
	LHFPL6	ENST00000855017.1		c.553+3403T>C		intron	N/A	ENSP00000525076.1

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105660 AN: 152070 Hom.: 37024 Cov.: 33

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.695 AC: 105722 AN: 152188 Hom.: 37044 Cov.: 33 AF XY: 0.701 AC XY: 52143 AN XY: 74406

African (AFR) AF: 0.601 AC: 24949 AN: 41532

American (AMR) AF: 0.772 AC: 11793 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2336 AN: 3464

East Asian (EAS) AF: 0.851 AC: 4400 AN: 5172

South Asian (SAS) AF: 0.785 AC: 3792 AN: 4828

European-Finnish (FIN) AF: 0.787 AC: 8352 AN: 10610

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47637 AN: 67988

Other (OTH) AF: 0.715 AC: 1505 AN: 2106

Alfa AF: 0.697 Hom.: 109866

Bravo AF: 0.692

Asia WGS AF: 0.801 AC: 2783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.71
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: rs1186468; hg19: chr13-39949162; COSMIC: COSV65448777;