rs62004863

Variant names:

• chr15-73907647-T-C
• rs62004863
• ENST00000804490.1:n.380+4538A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000804490.1(LOXL1-AS1):​n.380+4538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 152,292 control chromosomes in the GnomAD database, including 282 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 0.052 (282 hom., cov: 33)
• Consequence: LOXL1-AS1 ENST00000804490.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 0 publications found

Genes affected

LOXL1-AS1 (HGNC:44169): (LOXL1 antisense RNA 1)

TBC1D21 (HGNC:28536): (TBC1 domain family member 21) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Located in extracellular exosome. [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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D21	XM_011521281.4	c.979-2004T>C		intron_variant	Intron 10 of 10		XP_011519583.1
TBC1D21	XM_047432198.1	c.871-2004T>C		intron_variant	Intron 9 of 9		XP_047288154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1-AS1	ENST00000804490.1	n.380+4538A>G		intron_variant	Intron 3 of 3
LOXL1-AS1	ENST00000804491.1	n.430+4538A>G		intron_variant	Intron 3 of 3
LOXL1-AS1	ENST00000804492.1	n.455+4538A>G		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7898 AN: 152174 Hom.: 282 Cov.: 33

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.00846

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.0572

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0698

Gnomad OTH AF: 0.0647

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

GnomAD4 genome AF: 0.0519 AC: 7905 AN: 152292 Hom.: 282 Cov.: 33 AF XY: 0.0519 AC XY: 3868 AN XY: 74464

African (AFR) AF: 0.0179 AC: 745 AN: 41560

American (AMR) AF: 0.0532 AC: 813 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3470

East Asian (EAS) AF: 0.00848 AC: 44 AN: 5190

South Asian (SAS) AF: 0.0841 AC: 406 AN: 4826

European-Finnish (FIN) AF: 0.0572 AC: 607 AN: 10618

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0698 AC: 4748 AN: 68016

Other (OTH) AF: 0.0640 AC: 135 AN: 2110

Alfa AF: 0.0563 Hom.: 40

Bravo AF: 0.0482

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.65
DANN	Benign	0.68
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs62004863; hg19: chr15-74199988;