rs10216243

Positions:

• chr7-104873177-C-A
• chr7-104873177-C-G

Variant summary

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

The NM_199000.3(LHFPL3):​c.683-33010C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0876 in 152,238 control chromosomes in the GnomAD database, including 1,253 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 0.088 (1253 hom., cov: 32)
• Consequence: LHFPL3 NM_199000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

Genes affected

LHFPL3 (HGNC:6589): (LHFPL tetraspan subfamily member 3) 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. A partial gene fragment named LHFPL4 corresponds to a portion of the first exon of this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHFPL3	NM_199000.3	c.683-33010C>A		intron_variant		ENST00000424859.7	NP_945351.1
LHFPL3	NM_001386065.1	c.*31+27748C>A		intron_variant			NP_001372994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHFPL3	ENST00000424859.7	c.683-33010C>A		intron_variant		1	NM_199000.3	ENSP00000393128	P1
LHFPL3	ENST00000401970.3	c.*31+27748C>A		intron_variant		1		ENSP00000385374
LHFPL3	ENST00000683240.1	c.*290-33010C>A		intron_variant, NMD_transcript_variant				ENSP00000508253
LHFPL3	ENST00000684090.1	n.261-33010C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13312 AN: 152120 Hom.: 1252 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.0414

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0206

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0876 AC: 13331 AN: 152238 Hom.: 1253 Cov.: 32 AF XY: 0.0915 AC XY: 6809 AN XY: 74420

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.0673

Gnomad4 FIN AF: 0.0414

Gnomad4 NFE AF: 0.0206

Gnomad4 OTH AF: 0.0794

Alfa AF: 0.0405 Hom.: 167

Bravo AF: 0.0965

Asia WGS AF: 0.260 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.68

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: rs10216243; hg19: chr7-104513624;