chr11-94779904-T-C

Variant names:

• chr11-94779904-T-C
• rs12418045
• NM_130847.3:c.49+11344T>C

Variant summary

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

The NM_130847.3(AMOTL1):​c.49+11344T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 152,238 control chromosomes in the GnomAD database, including 479 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 0.050 (479 hom., cov: 33)
• Consequence: AMOTL1 NM_130847.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 2 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]

AMOTL1 Gene-Disease associations (from GenCC):

• orofacial cleft

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMOTL1	NM_130847.3	c.49+11344T>C		intron_variant	Intron 1 of 12	ENST00000433060.3	NP_570899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMOTL1	ENST00000433060.3	c.49+11344T>C		intron_variant	Intron 1 of 12	1	NM_130847.3	ENSP00000387739.2
AMOTL1	ENST00000317829.12	c.49+11344T>C		intron_variant	Intron 1 of 11	1		ENSP00000320968.8
AMOTL1	ENST00000299004.13	c.137-15107T>C		intron_variant	Intron 3 of 4	2		ENSP00000299004.9

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7622 AN: 152120 Hom.: 476 Cov.: 33

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.0790

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00900

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0502 AC: 7649 AN: 152238 Hom.: 479 Cov.: 33 AF XY: 0.0572 AC XY: 4257 AN XY: 74430

African (AFR) AF: 0.0559 AC: 2323 AN: 41538

American (AMR) AF: 0.122 AC: 1863 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1455 AN: 5182

South Asian (SAS) AF: 0.0799 AC: 385 AN: 4818

European-Finnish (FIN) AF: 0.0849 AC: 900 AN: 10598

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00900 AC: 612 AN: 68024

Other (OTH) AF: 0.0402 AC: 85 AN: 2114

Alfa AF: 0.0240 Hom.: 285

Bravo AF: 0.0560

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.44
PhyloP100		-0.017
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: rs12418045; hg19: chr11-94513070;