11-94725002-A-G

Variant names:

• chr11-94725002-A-G
• rs2068909
• ENST00000299004.13:c.-50-3919A>G

Variant summary

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

The ENST00000299004.13(AMOTL1):​c.-50-3919A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 152,240 control chromosomes in the GnomAD database, including 121 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 0.023 (121 hom., cov: 33)
• Consequence: AMOTL1 ENST00000299004.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• Publications: 1 publications found

Genes affected

AMOTL1 (HGNC:17811): (angiomotin like 1) The protein encoded by this gene is a peripheral membrane protein that is a component of tight junctions or TJs. TJs form an apical junctional structure and act to control paracellular permeability and maintain cell polarity. This protein is related to angiomotin, an angiostatin binding protein that regulates endothelial cell migration and capillary formation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

PIWIL4-AS1 (HGNC:55493): (PIWIL4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000299004.13. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIWIL4-AS1	NR_135093.1		n.138+15216T>C		intron	N/A
	PIWIL4-AS1	NR_135094.1		n.138+15216T>C		intron	N/A
	PIWIL4-AS1	NR_135096.1		n.138+15216T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMOTL1	ENST00000299004.13	TSL:2	c.-50-3919A>G		intron	N/A	ENSP00000299004.9	F8WDH4
	PIWIL4-AS1	ENST00000536540.5	TSL:3	n.52+15216T>C		intron	N/A
	PIWIL4-AS1	ENST00000537874.1	TSL:4	n.138+15216T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3427 AN: 152122 Hom.: 122 Cov.: 33

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00734

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0124

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

GnomAD4 genome AF: 0.0226 AC: 3439 AN: 152240 Hom.: 121 Cov.: 33 AF XY: 0.0217 AC XY: 1618 AN XY: 74426

African (AFR) AF: 0.0790 AC: 3283 AN: 41550

American (AMR) AF: 0.00727 AC: 111 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68008

Other (OTH) AF: 0.0123 AC: 26 AN: 2116

Alfa AF: 0.00642 Hom.: 44

Bravo AF: 0.0260

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.49
PhyloP100		-0.55
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: rs2068909; hg19: chr11-94458168;