rs11770570

Variant names:

• chr7-104330062-T-C
• rs11770570
• NM_199000.3:c.445+838T>C

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+838T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 152,294 control chromosomes in the GnomAD database, including 477 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 0.075 (477 hom., cov: 33)
• Consequence: LHFPL3 NM_199000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 2 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 = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL3	NM_199000.3	c.445+838T>C		intron_variant	Intron 1 of 2	ENST00000424859.7	NP_945351.1
LHFPL3	NM_001386065.1	c.445+838T>C		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+838T>C		intron_variant	Intron 1 of 2	1	NM_199000.3	ENSP00000393128.2
LHFPL3	ENST00000401970.3	c.445+838T>C		intron_variant	Intron 1 of 3	1		ENSP00000385374.3
LHFPL3	ENST00000683240.1	n.362+838T>C		intron_variant	Intron 1 of 3			ENSP00000508253.1

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11433 AN: 152176 Hom.: 470 Cov.: 33

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0602

Gnomad ASJ AF: 0.0904

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0390

Gnomad FIN AF: 0.0986

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.0707

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

GnomAD4 genome AF: 0.0753 AC: 11465 AN: 152294 Hom.: 477 Cov.: 33 AF XY: 0.0741 AC XY: 5514 AN XY: 74460

African (AFR) AF: 0.0635 AC: 2639 AN: 41566

American (AMR) AF: 0.0600 AC: 918 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0904 AC: 314 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0394 AC: 190 AN: 4822

European-Finnish (FIN) AF: 0.0986 AC: 1045 AN: 10596

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0891 AC: 6059 AN: 68030

Other (OTH) AF: 0.0699 AC: 148 AN: 2116

Alfa AF: 0.0845 Hom.: 956

Bravo AF: 0.0715

Asia WGS AF: 0.0250 AC: 88 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	2.0
DANN	Benign	0.57
PhyloP100		-0.64
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: rs11770570; hg19: chr7-103970510;