7-104477473-A-G

Variant names:

• chr7-104477473-A-G
• rs12666599
• NM_199000.3:c.445+148249A>G

Variant summary

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

The NM_199000.3(LHFPL3):​c.445+148249A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,168 control chromosomes in the GnomAD database, including 1,872 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 0.15 (1872 hom., cov: 32)
• Consequence: LHFPL3 NM_199000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.974
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL3	NM_199000.3	c.445+148249A>G		intron_variant	Intron 1 of 2	ENST00000424859.7	NP_945351.1
LHFPL3	NM_001386065.1	c.445+148249A>G		intron_variant	Intron 1 of 3		NP_001372994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL3	ENST00000424859.7	c.445+148249A>G		intron_variant	Intron 1 of 2	1	NM_199000.3	ENSP00000393128.2
LHFPL3	ENST00000401970.3	c.445+148249A>G		intron_variant	Intron 1 of 3	1		ENSP00000385374.3
LHFPL3	ENST00000683240.1	n.*52+79288A>G		intron_variant	Intron 2 of 3			ENSP00000508253.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23138 AN: 152050 Hom.: 1868 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.0994

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.152 AC: 23159 AN: 152168 Hom.: 1872 Cov.: 32 AF XY: 0.152 AC XY: 11344 AN XY: 74404

African (AFR) AF: 0.157 AC: 6495 AN: 41498

American (AMR) AF: 0.172 AC: 2630 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3466

East Asian (EAS) AF: 0.193 AC: 999 AN: 5178

South Asian (SAS) AF: 0.243 AC: 1171 AN: 4822

European-Finnish (FIN) AF: 0.0994 AC: 1054 AN: 10602

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9686 AN: 67994

Other (OTH) AF: 0.140 AC: 295 AN: 2114

Alfa AF: 0.148 Hom.: 6983

Bravo AF: 0.160

Asia WGS AF: 0.223 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		0.97
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: rs12666599; hg19: chr7-104117921;