chr8-30100300-G-A

Variant names:

• chr8-30100300-G-A
• rs12386822
• NM_015344.3:c.17-1598G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015344.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEPROTL1	NM_015344.3	MANE Select	c.17-1598G>A		intron	N/A	NP_056159.2
	LEPROTL1	NM_001128208.2		c.17-1598G>A		intron	N/A	NP_001121680.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEPROTL1	ENST00000321250.13	TSL:1 MANE Select	c.17-1598G>A		intron	N/A	ENSP00000314625.8
	LEPROTL1	ENST00000523116.5	TSL:2	c.17-1598G>A		intron	N/A	ENSP00000428281.1
	LEPROTL1	ENST00000520682.5	TSL:5	c.17-1598G>A		intron	N/A	ENSP00000429656.1

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

African (AFR) AF: 0.333 AC: 13783 AN: 41402

American (AMR) AF: 0.683 AC: 10427 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2386 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2078 AN: 5166

South Asian (SAS) AF: 0.578 AC: 2782 AN: 4816

European-Finnish (FIN) AF: 0.715 AC: 7531 AN: 10540

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47034 AN: 67980

Other (OTH) AF: 0.605 AC: 1278 AN: 2112

Alfa AF: 0.633 Hom.: 46994

Bravo AF: 0.568

Asia WGS AF: 0.500 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.66
PhyloP100		-0.81
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: rs12386822; hg19: chr8-29957816;