rs985409

Positions:

• chr7-104530976-A-G
• chr7-104530976-A-T

Variant summary

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

The NM_199000.3(LHFPL3):​c.445+201752A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,030 control chromosomes in the GnomAD database, including 11,541 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 0.38 (11541 hom., cov: 32)
• Consequence: LHFPL3 NM_199000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300

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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHFPL3	NM_199000.3	c.445+201752A>G		intron_variant		ENST00000424859.7	NP_945351.1
LHFPL3	NM_001386065.1	c.445+201752A>G		intron_variant			NP_001372994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHFPL3	ENST00000424859.7	c.445+201752A>G		intron_variant		1	NM_199000.3	ENSP00000393128	P1
LHFPL3	ENST00000401970.3	c.445+201752A>G		intron_variant		1		ENSP00000385374
LHFPL3	ENST00000683240.1	c.*52+132791A>G		intron_variant, NMD_transcript_variant				ENSP00000508253

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58395 AN: 151912 Hom.: 11533 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.384 AC: 58440 AN: 152030 Hom.: 11541 Cov.: 32 AF XY: 0.387 AC XY: 28760 AN XY: 74308

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.445

Alfa AF: 0.416 Hom.: 14902

Bravo AF: 0.378

Asia WGS AF: 0.407 AC: 1415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.9
DANN	Benign	0.48

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: rs985409; hg19: chr7-104171423;