8-30125002-T-C

Position:

• chr8-30125002-T-C

Variant summary

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

The NM_001128208.2(LEPROTL1):​c.280-12270T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,182 control chromosomes in the GnomAD database, including 52,795 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 0.83 (52795 hom., cov: 32)
• Consequence: LEPROTL1 NM_001128208.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

Genes affected

LEPROTL1 (HGNC:6555): (leptin receptor overlapping transcript like 1) Enables identical protein binding activity. Predicted to be involved in late endosome to vacuole transport via multivesicular body sorting pathway and negative regulation of growth hormone receptor signaling pathway. Predicted to be integral component of membrane. Predicted to be active in endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEPROTL1	NM_001128208.2	c.280-12270T>C		intron_variant			NP_001121680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEPROTL1	ENST00000523116.5	c.280-12270T>C		intron_variant		2		ENSP00000428281.1
LEPROTL1	ENST00000520682.5	c.280-6974T>C		intron_variant		5		ENSP00000429656.1
LEPROTL1	ENST00000442880.6	c.280-7373T>C		intron_variant		2		ENSP00000412803.2
LEPROTL1	ENST00000520739.5	n.279+20516T>C		intron_variant		4		ENSP00000429398.1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126445 AN: 152064 Hom.: 52760 Cov.: 32

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.831 AC: 126531 AN: 152182 Hom.: 52795 Cov.: 32 AF XY: 0.830 AC XY: 61749 AN XY: 74402

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.835

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.871

Gnomad4 OTH AF: 0.844

Alfa AF: 0.865 Hom.: 59591

Bravo AF: 0.830

Asia WGS AF: 0.828 AC: 2878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12681963; hg19: chr8-29982518;