rs12386822

Positions:

• chr8-30100300-G-A
• chr8-30100300-G-T

Variant summary

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

The NM_015344.3(LEPROTL1):​c.17-1598G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,968 control chromosomes in the GnomAD database, including 27,701 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 0.58 (27701 hom., cov: 32)
• Consequence: LEPROTL1 NM_015344.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LEPROTL1	NM_015344.3	c.17-1598G>A		intron_variant		ENST00000321250.13
LEPROTL1	NM_001128208.2	c.17-1598G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LEPROTL1	ENST00000321250.13	c.17-1598G>A		intron_variant		1	NM_015344.3	P1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88220 AN: 151850 Hom.: 27700 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.581 AC: 88233 AN: 151968 Hom.: 27701 Cov.: 32 AF XY: 0.582 AC XY: 43206 AN XY: 74276

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.605

Alfa AF: 0.673 Hom.: 32529

Bravo AF: 0.568

Asia WGS AF: 0.500 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.66

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: rs12386822; hg19: chr8-29957816;