rs5974264

Positions:

• chrX-112675997-C-T

Variant summary

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

The NM_178175.4(LHFPL1):​c.-15+3832G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 111,732 control chromosomes in the GnomAD database, including 597 homozygotes. There are 3,809 hemizygotes in GnomAD. 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 0.11 (597 hom., 3809 hem., cov: 23)
• Consequence: LHFPL1 NM_178175.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342

Genes affected

LHFPL1 (HGNC:6587): (LHFPL tetraspan subfamily member 1) 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]

LHFPL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHFPL1	NM_178175.4	c.-15+3832G>A		intron_variant		ENST00000371968.8	NP_835469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHFPL1	ENST00000371968.8	c.-15+3832G>A		intron_variant		1	NM_178175.4	ENSP00000361036.3
LHFPL1	ENST00000478229.1	n.226+3832G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 12320 AN: 111676 Hom.: 593 Cov.: 23 AF XY: 0.112 AC XY: 3807 AN XY: 33880

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0116

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.0492

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0717

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.110 AC: 12325 AN: 111732 Hom.: 597 Cov.: 23 AF XY: 0.112 AC XY: 3809 AN XY: 33946

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.0492

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0674

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0857 Hom.: 3561

Bravo AF: 0.125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.82

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: rs5974264; hg19: chrX-111919225;