ENST00000565689.6:n.590-1040A>C

Variant names:

• chr15-73909588-T-G
• rs12914677
• ENST00000565689.6:n.590-1040A>C

Variant summary

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

The ENST00000565689.6(LOXL1-AS1):​n.590-1040A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,918 control chromosomes in the GnomAD database, including 14,183 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 0.41 (14183 hom., cov: 31)
• Consequence: LOXL1-AS1 ENST00000565689.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D21	XM_011521281.4	c.979-63T>G		intron_variant	Intron 10 of 10		XP_011519583.1
TBC1D21	XM_047432198.1	c.871-63T>G		intron_variant	Intron 9 of 9		XP_047288154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1-AS1	ENST00000565689.6	n.590-1040A>C		intron_variant	Intron 4 of 4	3
LOXL1-AS1	ENST00000568229.6	n.418-1040A>C		intron_variant	Intron 3 of 3	2
LOXL1-AS1	ENST00000685373.2	n.519-1040A>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61665 AN: 151800 Hom.: 14184 Cov.: 31

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.406 AC: 61681 AN: 151918 Hom.: 14183 Cov.: 31 AF XY: 0.402 AC XY: 29871 AN XY: 74244

African (AFR) AF: 0.224 AC: 9299 AN: 41448

American (AMR) AF: 0.435 AC: 6638 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1698 AN: 3466

East Asian (EAS) AF: 0.0546 AC: 282 AN: 5166

South Asian (SAS) AF: 0.305 AC: 1467 AN: 4812

European-Finnish (FIN) AF: 0.513 AC: 5417 AN: 10556

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35474 AN: 67918

Other (OTH) AF: 0.392 AC: 822 AN: 2098

Alfa AF: 0.412 Hom.: 2755

Bravo AF: 0.393

Asia WGS AF: 0.182 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.69
PhyloP100		-0.88

Splicing

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

Other links and lift over

dbSNP: rs12914677; hg19: chr15-74201929;