NM_001128208.2:c.280-12270T>C

Variant names:

• chr8-30125002-T-C
• rs12681963
• NM_001128208.2:c.280-12270T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.98).
• 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 rank	MANE	Protein	UniProt
LEPROTL1	NM_001128208.2	c.280-12270T>C		intron_variant	Intron 3 of 3		NP_001121680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LEPROTL1	ENST00000523116.5	c.280-12270T>C		intron_variant	Intron 3 of 3	2		ENSP00000428281.1
LEPROTL1	ENST00000520682.5	c.280-6974T>C		intron_variant	Intron 3 of 3	5		ENSP00000429656.1
LEPROTL1	ENST00000442880.6	c.280-7373T>C		intron_variant	Intron 3 of 4	2		ENSP00000412803.2
LEPROTL1	ENST00000520739.5	n.279+20516T>C		intron_variant	Intron 3 of 5	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

African (AFR) AF: 0.745 AC: 30902 AN: 41490

American (AMR) AF: 0.876 AC: 13392 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2899 AN: 3470

East Asian (EAS) AF: 0.767 AC: 3969 AN: 5176

South Asian (SAS) AF: 0.867 AC: 4188 AN: 4832

European-Finnish (FIN) AF: 0.856 AC: 9060 AN: 10582

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.871 AC: 59220 AN: 68028

Other (OTH) AF: 0.844 AC: 1785 AN: 2114

Alfa AF: 0.863 Hom.: 87151

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
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12681963; hg19: chr8-29982518;