NM_199000.3:c.683-48956C>T

Variant names:

• chr7-104857231-C-T
• rs12705284
• NM_199000.3:c.683-48956C>T

Variant summary

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

The NM_199000.3(LHFPL3):​c.683-48956C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 150,144 control chromosomes in the GnomAD database, including 19,176 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 0.50 (19176 hom., cov: 32)
• Consequence: LHFPL3 NM_199000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793
• Publications: 5 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL3	NM_199000.3	c.683-48956C>T		intron_variant	Intron 2 of 2	ENST00000424859.7	NP_945351.1
LHFPL3	NM_001386065.1	c.*31+11802C>T		intron_variant	Intron 3 of 3		NP_001372994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL3	ENST00000424859.7	c.683-48956C>T		intron_variant	Intron 2 of 2	1	NM_199000.3	ENSP00000393128.2
LHFPL3	ENST00000401970.3	c.*31+11802C>T		intron_variant	Intron 3 of 3	1		ENSP00000385374.3
LHFPL3	ENST00000683240.1	n.*290-48956C>T		intron_variant	Intron 3 of 3			ENSP00000508253.1
LHFPL3	ENST00000684090.1	n.261-48956C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.498 AC: 74768 AN: 150026 Hom.: 19164 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.498 AC: 74798 AN: 150144 Hom.: 19176 Cov.: 32 AF XY: 0.498 AC XY: 36477 AN XY: 73226

African (AFR) AF: 0.355 AC: 14356 AN: 40416

American (AMR) AF: 0.514 AC: 7716 AN: 15020

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1781 AN: 3468

East Asian (EAS) AF: 0.509 AC: 2597 AN: 5098

South Asian (SAS) AF: 0.482 AC: 2274 AN: 4714

European-Finnish (FIN) AF: 0.518 AC: 5374 AN: 10366

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39056 AN: 67782

Other (OTH) AF: 0.487 AC: 1012 AN: 2078

Alfa AF: 0.546 Hom.: 92022

Bravo AF: 0.484

Asia WGS AF: 0.474 AC: 1652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		-0.79
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: rs12705284; hg19: chr7-104497678;